Bovine vaccines

Bovine vaccines

Proper vaccination is critically important for the control of infectious diseases in both beef and dairy cattle. With the growing increase in antibiotic resistance, improved vaccines are essential if bacterial diseases are to be effectively controlled. Disease prevention is of special importance in intensive feedlot and dairy operations, in addition to cow-calf operations with their high stocking density and low profit margins. Although carefully considered vaccination is important, other management issues such as nutrition, parasite control, and sanitation are also essential in controlling infectious diseases. Vaccines administered to breeding animals are designed to prevent reproductive losses, including infertility, embryonic death, abortion, and stillbirths. Vaccination of breeding cows is also critical in increasing the level of colostral antibodies and so ensuring that calves are protected. Calf vaccination is primarily designed to prevent deaths by respiratory and diarrheal diseases. As in other species, it is usual to use combined vaccines with multiple antigenic components, especially for the control of bovine respiratory disease. Core vaccine recommendations may be modified in relation to the nature of the cattle operation in addition to the degree of exposure to other cattle from multiple sources and any stresses that the animals might be under such as transportation, castration, and weaning. It should also be emphasized that not all vaccines are cost-effective. There is no point in vaccinating animals against diseases that do not occur in the herd, region, or state (Tables 16.1, 16.2, and 16.3).

TABLE 16.1 ■

Vaccination of Calves Under 1 Year

Vaccine/Disease Vaccine Timing Comments
Bacterial Diseases
Mannheimia haemolytica Calves vaccinated under 6 months should be revaccinated after 6 months or at weaning. Ideally these vaccines should be boosted at least 2–3 weeks before weaning, shipping, or other stresses. Revaccinate on arrival. Usually combined with the other respiratory pathogens, BVD IBR, BRSV, and PI3, and also clostridial vaccines.

Withdrawal time 21 days.

Histophilus somni Given at the same time as the M. hemolytica bacterin. Vaccinate calves 3–6 months of age. Revaccinate in 3 weeks. Calves vaccinated under 6 months should be revaccinated after 6 months or at weaning. Usually combined with the other respiratory pathogens, BVD IBR, BRSV, and PI3. Revaccination is need based.

Withdrawal time 21 days.

Leptospirosis Vaccinate at 12 weeks. Revaccinate 4–6 weeks later and at 3–6 months of age. Semiannual revaccination may be required.

Withdrawal time 21 days.

Clostridial mixed bacterins and bacterin-toxoids. Two doses are required 3–6 weeks apart. Vaccinate calves at marking and revaccinate at weaning (60–90 days). Withdrawal time 21–60 days.
Brucella abortus Vaccinate healthy heifers with RB51 vaccine between 4–12 months. Must be given by an accredited veterinarian. Withdrawal time 21 days.
Salmonella Vaccinate calves over 2 weeks of age. Revaccinate 2 weeks later. Injections on opposite sides of the neck.

Withdrawal time 21–60 days.

Fusobacterium necrophorum To prevent footrot, vaccinate calves older than 6 months. Revaccinate 21 days later. For the prevention of liver abscesses vaccinate on arrival at the feedlot and revaccinate 60 days later. Meat withdrawal time 21 days.
Infectious bovine keratitis

Pinkeye. M. bovis and M. bovoculi

Vaccinate calves over 2 months of age, ideally 3–6 weeks before the fly season. Withdrawal time 21–60 days.
Johne’s Disease

Mycobacterium avium paratuberculosis

Vaccinate calves over 35 days. Given in the brisket/dewlap area. Only with state approval. Hazardous to humans.

Meat withdrawal time 60 days.

Viral Diseases
Infectious bovine rhinotracheitis Vaccinate in combination with BVD and PI3 2–4 weeks before weaning at 3–6 months. Revaccinate 1 month after weaning. Calves vaccinated before 6 months should be revaccinated after 6 months. Vaccinated on entering a feedlot or the dairy.

Withdrawal time 21days.

Bovine virus diarrhea Vaccinate 2–4 weeks before weaning. Withdrawal time 21–60 days.
Parainfluenza 3 Vaccinate 2–4 weeks before weaning. Withdrawal time 21–60 days.
Bovine respiratory syncytial virus Vaccinate 2–4 weeks before weaning. Withdrawal time 21–60 days.
Rota and coronavirus Vaccinate neonatal calves 30 minutes before allowing the calf to suckle because the colostral antibodies will inactivate it. Some veterinarians prefer to vaccinate the pregnant cow and rely on colostral immunity.

Withdrawal time 21–60 days.

Rabies Vaccinate cattle between 12 weeks and 3 months. Annual revaccination.

Withdrawal time 21 days.


These tables are examples of consensus vaccination programs. Individual programs may vary greatly and reflect animal health, local environmental and housing conditions, severity of challenge and disease prevalence in addition to professional judgment. Be sure to follow the manufacturer’s recommendations on the label.

All withdrawal times are for meat unless otherwise stated.

TABLE 16.2 ■

Vaccine/Disease Vaccine Timing Comments
Bacterial Diseases
Mannheimia haemolytica Annual revaccination if necessary. Withdrawal time 21 days.
Histophilus somni Annual revaccination if necessary. Withdrawal time 21 days.
Leptospirosis Vaccinate 30–60 days before breeding.

Revaccinate at 3–4 weeks and 5 and 2 weeks before breeding. The herd should be vaccinated 60 and 30 days before the breeding season and again when pregnancy is assessed. Revaccinate in the fall with a booster 4–6 weeks later. Replacement heifers require 2 doses of Leptospirosis and Campylobacter bacterins.

Annual revaccination, but more often in endemic situations. Also use on animals entering the herd.

Withdrawal time 21 days.

Clostridia 7–8-way combination. Vaccinate cattle over 6 months. Calves vaccinated under 3 months of age should be revaccinated at 6 months. Also vaccinate heifers prebreeding and precalving. Annual revaccination.

Withdrawal time 21 days.

Campylobacter (Vibriosis) Vaccinate heifers 30 to 60 days before breeding. Revaccinate in 3–4 weeks and on entering the herd. Vaccinate bulls prebreeding. Annual revaccination.

Withdrawal time 21–60 days depending on the vaccine.

Salmonella Vaccinate with two doses at 14–21 day intervals. Withdrawal time 21–60 days.
Footrot and liver abscesses (Fusobacterium) Vaccinate cattle over 6 months. Revaccinate in 3–6 weeks. Revaccinate annually if risk persists.

Withdrawal time 21 days.

Anthrax Vaccinate using two doses in known enzootic areas 2–3 weeks apart. Annual revaccination before the time the disease is expected.

Withdrawal time 42 days.

Infectious bovine keratitis (Pinkeye) Vaccinate cattle over 2 months of age. Revaccinate in 3–4 weeks or at weaning, ideally 3–6 weeks before the fly season. Annual revaccination if needed.

Withdrawal time 21–60 days.

Johne’s Disease Vaccinate only replacement heifers, and bull calves between 1 and 35 days of age. Only with state approval. Withdrawal time 60 days.
Viral Diseases
Infectious bovine rhinotracheitis Vaccinate 1 month before breeding heifers.

Vaccinate replacement heifers 30–60 days before breeding. Vaccinate bulls before breeding.

Annual revaccination.

Withdrawal time 21–60 days.

Bovine virus diarrhea Vaccinate 1 month before breeding. Vaccinate replacement heifers 30–60 days before breeding. Vaccinate bulls before breeding. Annual revaccination. Withdrawal time 21–60 days.
Parainfluenza 3 Vaccinate 1 month before breeding. Vaccinate replacement heifers 30–60 days before breeding. Vaccinate bulls before breeding. Annual revaccination. Withdrawal time 21–60 days.
Respiratory syncytial virus Vaccinate 1 month before breeding. Vaccinate replacement heifers 30–60 days before breeding. Vaccinate bulls before breeding. Annual revaccination. Withdrawal time 21–60 days.
Protozoan diseases
Trichomoniasis Vaccinate with two doses 2–4 weeks apart. Complete by 4 weeks ahead of the breeding season. Annual revaccination.

Withdrawal time 60 days.


These tables are examples of consensus vaccination programs. Individual programs may vary greatly and reflect animal health, local environmental and housing conditions, severity of challenge, and disease prevalence, in addition to professional judgment. Be sure to follow the manufacturer’s recommendations on the label.

All withdrawal times are for meat unless otherwise stated.

TABLE 16.3 ■

Vaccination of Pregnant Cows

Vaccine/Disease Vaccine Timing Comments
Bacterial Diseases
Clostridia Vaccinate 2–3 weeks precalving. Withdrawal time 21 days.
Campylobacter Vaccinate breeding animals twice before the breeding season. Vaccinate bulls twice annually, 3 weeks apart, with the last dose 2 weeks before the breeding season. Cows should be revaccinated about halfway through the breeding season. Withdrawal time 21–60 days.
Salmonella Vaccinate cows 4–6 weeks before calving. Withdrawal time 21–60 days.
Colibacillosis Vaccinate cows twice with the final dose 4–3 weeks before calving. Withdrawal time 21–60 days.
Viral Diseases
IBR, BVD, PI3, and BRSV To prevent IBR-induced abortion and BVD-persistently infected calves ensure that cows have been completely vaccinated before breeding. Use modified live vaccines in these immune cows only if they are approved for this purpose. Inactivated vaccines may be used without prior protection. Withdrawal time 21–60 days.
Rota and coronavirus Vaccinate healthy pregnant cows 3 months before calving. Revaccinate in 3–6 weeks. These may be combined with other vaccines such as Escherichia coli or Clostridium perfringens. These may also be given to neonatal calves. Revaccination in subsequent pregnancies should be based on the presence of the infection.

Withdrawal time 21 days.


These tables are examples of consensus vaccination programs. Individual programs may vary greatly and reflect animal health, local environmental and housing conditions, severity of challenge and disease prevalence in addition to professional judgment. Be sure to follow the manufacturer’s recommendations on the label.

All withdrawal times are for meat unless otherwise stated.

Vaccine administration

Beef quality assurance guidelines are concerned with physical damage to meat sold to the consumer. Injection site lesions such as bruising, abscesses, or broken needles, causing carcass blemishes or worse, are of major concern. Although not all such lesions are caused by vaccination, they must be minimized. Clostridial vaccines are known to be especially irritating. Intramuscular vaccination presents the greatest risk. Needle damage, deposition of foreign material, local inflammation, and scarring are all possible results. Scars may persist for up to 300 days following injection. Abscess formation with fluid or pus-filled cavities is the most obvious of these problems (Fig. 16.1). A second common form of damage is a dry, sterile, scarred woody-looking pale area in the muscle. Although mild, these lesions still require trimming at processing. They are especially important if they are located in the rump where the meat is not usually ground but used as whole meat products. In some cases, these lesions may not be detected until the consumer has cut into it. Otherwise the meat has to be trimmed to remove these lesions. Muscles from the hind legs of carcasses have been examined for the frequency of injection site lesions. These range from 60% to 35% in dairy cattle and from 31% to 20% in beef cattle. The difference is probably because of the fact that more dairy cattle than beef cattle are given vaccines. These lesions are estimated to cost the beef industry over US$4 million annually.

Injection site lesions are most likely to occur when cattle are injected from behind while their heads are restrained. The preferred sites for bovine vaccination are in the neck muscle in front of and behind the shoulder. Veterinarians should avoid intramuscular injections if other inoculation routes are available. Subcutaneous products should be inoculated into pinched “tented” skin. Intramuscular injections should be injected straight and deep into the muscle. Good sanitation is absolutely essential. When using killed vaccines, alcohol sponges may be used to clean needles between injections. This is not appropriate if using modified live vaccines.

Antibacterial vaccines

Bovine respiratory disease complex

Bovine respiratory diseases (BRD) and undifferentiated fevers are estimated to cost the North American cattle industry up to US$1 billion each year. From 2011 to 2015, BRD in preweaned calves cost the US cow-calf industry about US$165 million annually. It is equally significant in other cattle-producing countries. BRD has a complex etiology and its occurrence depends upon age, weight, origins (ranch or sales barn), genetics, environmental problems, and stresses such as transportation, weaning, and overcrowding in addition to exposure to potential pathogens. In general, stress causes immunosuppression that permits viral infection that is followed by secondary bacterial invasion of the respiratory tract. The common viruses involved in BRD include bovine herpesvirus 1 (BHV-1), parainfluenza 3 (PI3), bovine respiratory syncytial virus (BRSV), and bovine virus diarrhea virus (BVDV). Other viruses that may be involved include bovine coronavirus, enteroviruses, and reoviruses. Bacterial pathogens may include Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, and Histophilus somni. Because of the complex pathogenesis of BRD, combined vaccines containing multiple antigens are usually used to control these pathogens. Combination vaccines may contain antigens against the five major respiratory viruses: BVD types 1 and 2, BRSV, BHV-1, and PI3. Mannheimia, Pasteurella, Histophilus, Campylobacter, and Leptospirosis antigens may also be added to these vaccine mixtures.

When calves arrive at a feedlot, the initial processing usually includes vaccination for the common bacterial and viral organisms associated with shipping fever. However, pneumonia often develops within two weeks after arrival before these vaccines have had sufficient time to confer immunity. Ideally these vaccines should be given at least two to three weeks before shipping to the feedlot. They can then be boosted on arrival.

Mannheimia haemolytica

M. haemolytica is the predominant bacterium found in bovine pneumonic lesions. This is commonly M. haemolytica serotype 1, but there are at least 12 other bacterial serotypes based on their capsular antigen structure. Protective immunity to M. haemolytica requires the development of neutralizing antibodies against its leukotoxin and its outer membrane proteins. Most M. haemolytica vaccines are therefore of the bacterin-toxoid type. These vaccines are also effective against the related respiratory pathogen Bibersteinia trehalosi.

Pasteurella multocida

P. multocida subgroup A is a gram-negative bacterium commonly found in the bovine upper respiratory tract where it can act as a commensal or as a pathogen. When BRD develops as a result of environmental changes and stresses such as transportation or overcrowding, P. multocida is commonly isolated from the lesions. Immunity is presumed to be antibody-mediated. The bacterial leukotoxin is a major protective antigen. Available vaccines include bacterin-toxoids and a live streptomycin-dependent attenuated strain. These are usually administered as combined vaccines that also contain M. haemolytica and other BRD-associated pathogens.

Histophilus somni

H. somni is commonly isolated from BRD cases. In addition to respiratory disease it causes septicemia with vasculitis, thrombotic meningoencephalitis, myocarditis, arthritis, and it localizes in the uterus to cause abortion. It acts synergistically with bovine respiratory syncytial virus. H. somni also undergoes some antigenic variation that probably explains its persistence in infections. It is an extracellular organism that can be controlled by antibodies against the bacterial outer membrane proteins. An alum adjuvanted bacterin is available against H. somni. This may be administered as a combined bacterin with Clostridia and diverse other respiratory pathogens (see Table 16.1). The efficacy of these bacterins is unclear because it is difficult to reproduce pure H. somni-mediated disease experimentally. As pointed out, calves should be vaccinated before entering the feedlot because vaccination on entry may be too late.


This disease is caused by multiple Leptospira serovars and spreads through a herd via animal contact and contaminated water. The most important of these serovars are Leptospira borgpetersenii serovar, Hardjo-bovis, and Leptospira interrogans serovars, Hardjo and Pomona. The acute disease causes agalactia, icterus, and hemoglobinuria. The chronic disease results in abortions, stillbirths, and weak calves.

Multivalent killed adjuvanted Leptospira bacterins are available. Of the 55 licensed Leptospira combination vaccines currently available in the United States, all contain Pomona, 36 contain Hardjo, and 23 contain Hardjo-bovis. These provide immunity against disease caused by most serovars with the possible exception of serovar Hardjo. However, as with all Leptospira bacterins, the immune response is directed against the bacterial lipopolysaccharide. As a result, immunity is strain-specific and is not long lasting. Even under the best of conditions these do not provide protection for much longer than six months. Other serovars occasionally implicated in cattle include Grippotyphosa, Bratislava, and Icterohaemorrhagiae.

Clostridial vaccines.

A wide diversity of clostridial vaccines are available for use in cattle (see Table 16.2). They may be administered singly or in many combinations. They may contain toxoids or bacterin-toxoids. Commercial vaccines may contain multivalent 2-, 4-, 7-, 8-way or even 9-way combinations of bacterins and toxoids. In general, these combinations contain a mixture of clostridia, especially Clostridium tetani, Clostridium chauvoei (blackleg), Clostridium septicum (malignant edema), Clostridium haemolyticum (bacillary hemoglobinuria), Clostridium novyi type B (black disease), Clostridium sordellii, and Clostridium perfringens types C and D (enterotoxemia). Interestingly, it is conventional to consider that these 8 organisms constitute a “9-way” vaccine, because the combination of Cl. perfringens types C and D also protects against Cl. perfringens type B toxin.

Tetanus vaccination is essential, especially when castrating older calves and using bands. It too may be administered in combination products to cattle, sheep, and goats. A common vaccine combines Cl. tetani with Cl. perfringens types C and D. Feedlot cattle may receive a 4-way vaccine combining Cl. chauvoei, Cl. novyi, Cl. septicum, and Cl. sordellii for the prevention of blackleg and malignant edema. Addition of Cl. perfringens will also protect against enterotoxemia and addition of Cl. haemolyticum will protect against necrotic hepatitis. These vaccines may cause significant local reactions so it is important to administer them subcutaneously in the neck. Pregnant cows may also be vaccinated to maximize maternal antibody levels in colostrum (see Table 16.3). These antibodies may block effective anticlostridial responses in calves until they are at least two to three months of age.


Brucella abortus causes abortions, reduced milk yield, and infertility. It has been controlled in North America and Europe by a vaccination, test, and slaughter program. Brucellae are facultative intracellular bacteria and as a result they cannot be effectively controlled by antibodies alone. Antibodies may influence the initial phase of infection, but once the organisms enter cells, they can only be controlled by T cell-mediated macrophage activation. Cell-mediated immune responses are therefore essential and this means that only live organisms can serve as effective vaccines. Unfortunately, none of these live vaccines are entirely satisfactory.

Brucella abortus strain 19 vaccine

Strain 19 is a very widely used modified live vaccine and the standard by which all others are judged. It is usually given to 4- to 12-month-old heifers in a single subcutaneous injection containing 7 to 10 × 109 viable bacteria; vaccination of bull calves is not recommended. A reduced dose of 3 × 108 to 5 × 109 bacteria may be given to adult cows, but they may abort and secrete the organism in their milk. The vaccine may also be given to cattle by the conjunctival route. S19 produces good immunity against moderate challenge by B. abortus and Brucella melitensis. However, it must be administered by an accredited veterinarian and vaccinated animals must be identified by an ear tag and a tattoo. The main disadvantage of S19 is that it has a smooth phenotype, and as a result induces antilipopolysaccharide antibodies. These are detected by conventional agglutination tests, and as a result it is difficult to distinguish vaccinated from infected animals.

Brucella abortus strain RB51

RB51 is the brucellosis vaccine strain currently licensed for the protection of cattle against Brucellosis in the United States. It is a stable spontaneous rifampin-resistant rough mutant that lacks the O-polysaccharide side chain because of a mutation in its wboA glycosyl transferase gene. As a result, RB51 does not induce the antibodies against the smooth polysaccharide that cause false-positive agglutination tests. It is as effective as S19 but less likely to cause abortions. Immunosuppression will not cause its recrudescence. Unfortunately, full doses of RB51 may still invade the placenta, and fetus and so cause abortions. The organism also invades the mammary gland and may be excreted in the milk. Even with a reduced dose RB51 may still be shed by a few vaccinated animals. Like S19, it must be administered by an accredited veterinarian. Vaccination of high-risk animals over 12 months of age requires special authorization from state or federal animal health officials. Vaccinated animals must be identified by an ear tag and a tattoo. Although still infectious for humans, RB51 is less virulent than S19.


This is a sexually transmitted ascending infection caused by Campylobacter fetus subspecies venerealis. It is spread by infected bulls. C. fetus causes infertility, embryonic death, and abortion. The infection is usually self-limiting, but animals may remain infected for many months. Some infected cows may have a normal calf but still remain persistently infected. As a result, they may continue to infect bulls and so allow the infection to persist from year to year. Infections with C. fetus subspecies fetus also cause abortions but tend to be more sporadic.

A formalin-killed, oil-adjuvanted bacterin is available against C. fetus. It provokes an antibody response in the serum, uterus, and vagina. This vaccine should be given at weaning, when cows are palpated, and then revaccinated annually. Breeding bulls must also be vaccinated eight and four weeks before the breeding season and annually thereafter.


Bovine salmonellosis is a matter of public health concern and also an economically important infection. Although it may affect cattle of all ages, it is of greatest significance in calves under 10 weeks of age. The most common serotypes are Typhimurium and Dublin. They are responsible for acute diarrhea in calves and multisystemic illness in adult cattle in addition to invasive septicemia. Even when not clinically apparent, Salmonellae may be carried by healthy cattle and transmitted to humans through meat or milk products. It is important therefore to control Salmonella-mediated disease in addition to the carriage and shedding of these organisms. Killed bacterins and modified live vaccines have both been employed. As expected, the live vaccines usually give better protection than the killed ones. A rough mutant of serotype Dublin (EnterVene-d, Boehringer Ingelheim) is the most widely employed live vaccine. An SRP vaccine using siderophore receptor and porin proteins is also available. It reduces the shedding of serotype Newport in dairy cattle.


Enteric colibacillosis caused by enteropathogenic Escherichia coli in neonatal calves is a significant disease and a major cause of economic loss. It commonly occurs in calves 2 to 10 days after birth but may begin as early as 12 hours. In addition to hygiene, good nutrition, and stress issues, its occurrence is linked to insufficient colostrum intake. Because of its very early onset it must be largely controlled by vaccination of pregnant cows and the induction of colostral antibodies. Available bacterins contain enterotoxic E. coli possibly supplemented by the addition of F5 (K99) adherence pili. These are usually administered to pregnant cows in two doses three to four weeks before calving. Revaccination is recommended at each subsequent pregnancy. A polyclonal equine anti F5 serum is available for the oral treatment of neonatal calves. Note that vaccination is only one part of a comprehensive management strategy to control calf scours.

A vaccine against E. coli O157 is also available for use in cattle. Its function is to reduce the carriage rate of this significant human pathogen. It is administered to cattle over five months of age. Given the importance of cattle in the transmission of this organism, the vaccine, if used, is likely to cause a significant drop in the prevalence of this infection.


Caused by Anaplasma marginale, a member of the order Rickettsiales, this infection results in anemia, jaundice, and sudden death. An experimental killed vaccine has been approved by US Department of Agriculture (USDA) and is used in several US states. It contains purified Anaplasma cell bodies with adjuvant and is administered subcutaneously. Because it does not contain red cell proteins it does not induce neonatal isoerythrolysis (Chapter 10).

Attenuated live vaccines are available is some countries and were marketed in the United States until 1999. These consisted of chilled or frozen infected bovine blood. They were expensive, required annual boosters, and their use raised significant safety issues, because other infections in the donor animals could be disseminated through many recipients. Because the organisms in the vaccine were live, they induced clinical reactions that had to be treated with tetracycline or imidocarb. A live frozen vaccine is currently available in California. It is given to cattle under 11 months of age.

In some countries, a related avirulent species, Anaplasma centrale, is used as a vaccine against Anaplasma marginale. In these cases, a susceptible splenectomized calf is infected and when the bacteremia is high, it is bled and its blood used as a vaccine. Because it contains bovine red cells, this vaccine has the potential to cause hemolytic disease of the newborn in calves from vaccinated cows (yellow calf disease) (Chapter 10).


Bovine footrot is a bacterial infection of the hoof and interdigital skin caused by a complex of anaerobic gram-negative bacteria, including Fusobacterium necrophorum, Porphyromonas levii, and Prevotella intermedia. F. necrophorum also causes liver abscesses in cattle. A bacterin is available in North America against F. necrophorum. (Fusoguard, Elanco). It is used for the prevention of both footrot and liver abscesses. (See Chapter 17.) Footwarts (papillomatous interdigital dermatitis) can be a serious problem in dairy cattle. The cause is believed to be spirochetes of the genus Serpens. An adjuvanted bacterin is available against these organisms. It should be used in association with appropriate management procedures.

Infectious bovine keratoconjunctivitis (pinkeye)

Pinkeye is a severe conjunctivitis caused by the bacteria Moraxella bovis, Moraxella bovoculi, and Moraxella ovis. It is not uncommon to find other bacteria in eye lesions as well. These organisms attach to the cornea through their pili and trigger severe inflammation, resulting in corneal edema, ulceration, and partial or total blindness. Consequently, there is a drop in feed intake, body condition, and milk yield. The initial attachment of M. bovis to corneal cells is mediated through the Q pilus, but persistent attachment is caused by the bacterial I pilus. Thus bacterins should contain both pilus antigens. An effective bacterin is available against M. bovis and there is a multivalent bacterin available against M. bovoculi as well. They may be combined with clostridial vaccines.

In the United States, a Moraxella vaccine is also available for implantation in pellet form. Two pellets are inoculated at one time under the skin at the base of the ear or in the neck. One pellet is designed for immediate antigen release to promote rapid protection. It rehydrates rapidly and begins antigen release at once. The other pellet rehydrates slowly and releases Moraxella antigens over a two to three week period. It is thus designed for prolonged antigen release, effective boosting, and longer-term immunity. Because of the diversity of bacterial strains involved, autogenous vaccines are often used for this disease.

Mycobacterium avium, subspecies paratuberculosis

Mycobacterium avium, subspecies paratuberculosis (MAP) is the cause of Johne’s disease, a chronic enteritis that results in a drop in milk yield, significant weight loss, and decrease in body condition. In the United States, MAP-positive herds lose almost US$100/cow and production losses may reach US$200 to US$250 million. Many vaccines have been developed in different countries for this disease. These included heat-killed bacterins, live attenuated vaccines incorporated with oil and pumice powder, and lyophilized live attenuated vaccines combined with oil adjuvants.

A single paratuberculosis vaccine (MAP strain 18) is available in the United States (Mycopar, Boehringer Ingelheim). Interestingly the organism in this vaccine is not a MAP but Mycobacterium avium serovar 2. It is a whole cell bacterin suspended in oil and it is injected into the dewlap. The withdrawal time for this product is 60 days.

The use of MAP vaccines carries several risks. The oil adjuvant can induce a granulomatous reaction at the injection site—most are small and painless. Similar vaccines in other countries may be more reactogenic. Granulomas may become abscessed and leak. Accidental self-inoculation of humans may also cause severe acute reactions with tissue sloughing and chronic synovitis. If this occurs, the victim should seek immediate medical attention and the oil removed by suction or excision.

MAP vaccine may only be administered by a veterinarian who has been approved by state health officials. The herd owner and the veterinarian must enter an agreement with the state veterinarian regarding its use. Three conditions must be met before this can be done. First, it must be confirmed that the premises are actually infected with MAP either by isolating the organism or detecting it by polymerase chain reaction (PCR). Second, all the animals in the herd must have a negative tuberculin test and replacement stock must also be tuberculosis free. Third, the owner and the state animal health authorities must sign an agreement regarding its use.

Only replacement heifers and bull calves between 1 and 35 days of age may be vaccinated. Vaccinated calves must have external identification and a tattoo indicating that they have been vaccinated against Johne’s disease.

Vaccinated cattle develop a delayed hypersensitivity that may result in a false positive caudal fold skin test for tuberculosis. In such cases confirmatory comparative cervical tests must be performed, using bovine and avian tuberculin. The M. avium response should be much greater than the response to M. bovis. In a large herd the cost of this can be significant and the herd must be quarantined until its true TB status is clarified. As a result, many states do not permit MAP vaccination.

Although this vaccine may not prevent new infections, much depends on the age of the cattle, the level of mycobacterial contamination, and herd management standards. It generally reduces clinical disease, fecal shedding, and MAP burden. These factors, plus an increase in herd immunity, should reduce herd transmission.

In countries such as Australia, ovine Johne’s disease is a significant problem, and there is widespread use of a heat killed, mineral oil adjuvanted MAP vaccine (MAP strain F316, Gudair, Zoetis). It appears to be very effective in sheep and goats. A similar vaccine (Silirum Zoetis), is used in young farmed deer in New Zealand.

Bacille Calmette-Guerin (BCG) vaccine, an attenuated strain of Mycobacterium bovis, is of limited effectiveness in protecting humans against tuberculosis, but can protect cattle against M. bovis with 55% to 86% efficacy. Its developers, Calmette and Guerin demonstrated this in 1911. Low dose BCG (3 × 105 organisms) has been used successfully to control tuberculosis in free-ranging cattle in New Zealand. Unfortunately, the conventional dose of BCG (108–1010 organisms) sensitizes cattle resulting in positive tuberculin skin tests and cannot therefore be used routinely.

Antiviral vaccines

Infectious bovine rhinotracheitis

Bovine herpesvirus 1 (BHV-1), a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, causes reproductive, respiratory, enteric, and neurologic disease in cattle. The infection is characterized by upper respiratory tract disease with a purulent nasal discharge, hyperemia of the muzzle and conjunctivitis. Systemic disease causes abortions in nonimmune pregnant cows and may result in a loss of up to 60% of fetuses. The virus can also invade the genital tract to cause pustular vulvovaginitis. BHV-1 plays a significant role in the bovine respiratory disease complex.

Inactivated and modified live BHV-1 vaccines are available. As with all herpesvirus vaccines they can reduce clinical signs and reduce viral shedding but cannot completely prevent infection. Viral DNA persists in the sensory ganglia of its hosts for life.

Inactivated vaccines contain virus or purified viral glycoproteins and are adjuvanted. They are given subcutaneously or intramuscularly. Although inactivated vaccines do not induce a long-lasting response and vaccinated animals are slow to develop immunity, they can be given safely to pregnant cows. BHV-1 glycoprotein E or -D-deleted attenuated mutants are available and can be used as components in a DIVA strategy.

A temperature sensitive (ts), cold-adapted strain of BHV-1 is also available to be administered intranasally. This vaccine induces a rapid protective response, within 24–48 hours of administration. However, it may also induce mild respiratory disease and a drop in milk production.

An attenuated BHV-1 field strain passaged in tissue culture has generated small plaque variants. These variants proved to have lost the genes for gE and US9. These are the basis of current DIVA vaccines. A thymidine kinase deleted (TK) BHV-1 vaccine has also been developed. It appears to be very safe but, like other herpesvirus vaccines, is unable to prevent latent infections.

Bovine virus diarrhea

Bovine virus diarrhea viruses (BVDVs) are Pestiviruses in the family Flaviviridae. This genus contains four important livestock pathogens: BVDV1, BVDV2, classical swine fever, and border disease virus. A new species called “HoBi-like” or BVDV3 has been identified in South America and Asia. The two BVD viruses have multiple subgenotypes (15 in BVDV1 and 2 in BVDV2). They induce enteric, respiratory, and reproductive diseases in cattle. BVDV includes two distinct biotypes: cytopathic (cp) and noncytopathic (ncp). (The name describes their behavior in cell culture, not their pathogenicity in animals.) Ncp strains suppress type I interferon (IFN) production but permit type III (IFN-λ) production by dendritic cells. The type III interferon suppresses some T cell subsets and enables the virus to cause persistent infections. Cp strains, in contrast, induce type I IFN production and do not cause persistent infections. Ncp BVD infections occurring in pregnant cows between 50 and 120 days postconception, before the fetus develops immune competence, result in asymptomatic persistent infection (PI) because the fetal calves develop tolerance to the virus. Once born, these PI calves remain viremic, yet because of their tolerance they do not make antibodies or T cells against BVDV. Some of these calves may show minor neurologic problems and failure to thrive, some die suddenly, but many are clinically normal. These persistently infected calves grow slowly and often die of opportunistic infections such as pneumonia before reaching adulthood (BVDV has a tropism for T cells and is therefore immunosuppressive). Because they are tolerant to BVDV, persistently infected calves can shed large quantities of the virus in their secretions and excretions.

The cp strains, however, can cause mucosal disease (MD), a severe enteritis resulting in profuse diarrhea, dehydration, and death. Mucosal disease results from a mutation in the gene that controls the BVDV biotype while the animal fails to produce neutralizing antibodies or T cells. The cp strain can spread between tolerant animals and lead to mucosal disease outbreaks.

Recombination may occur between persistent wild-type ncp strains and vaccine cp strains and this may also cause MD. Some of the lesions in MD are attributable to the direct pathogenic effects of BVDV, but glomerulonephritis and other immune-complex–mediated lesions also develop. Because persistently infected calves can reach adulthood and breed, it is possible for BVDV to persist indefinitely within carrier animals and their calves.

Preventing disease and limiting viral spread motivate vaccination of young cattle. Vaccination of reproductive age cattle is intended to prevent viremia and the birth of persistently infected calves. Currently almost all inactivated BVDV vaccines contain both BVDV1a, and BVDV2a. Most contain cp strains for safety reasons (they will not cause persistent infection), whereas some may also contain an ncp strain. Although very safe, these vaccines are relatively ineffective and require multiple boosters to induce protection. Inactivated vaccines usually generate antibodies by three to four weeks after a single dose and antibody levels peak by about six weeks. Onset of immunity may be delayed in some animals for four to six weeks, resulting in a period of susceptibility. There appears to be significant variation in effectiveness of different commercially available vaccines.

Modified live vaccines (MLVs) stimulate much higher levels of antibodies than do inactivated ones, and also stimulate cell-mediated immunity. Protection may develop as soon as three to five days following vaccination with MLVs. They reduce viremia and nasal shedding in addition to preventing disease and mortality. There is little field evidence to suggest that MLV cp strains can cause mucosal disease, but a recent report described MD in cattle after vaccination with BVDV1a and -2a and the gene sequence of the isolated virus resembled the vaccine strain. At least one BVD-MLV vaccine has been shown to induce a leukopenia and suppress the lymphocyte response to mitogens as a result of a drop in T cell numbers,

Cows and replacement heifers should be vaccinated before the breeding season whereas calves should be vaccinated at weaning. Maternal antibodies to BVDV persist for 5 to 6 months or longer in dairy calves (see Fig. 8.2). (Evidence suggests that while maternal antibodies block antibody responses, calves may develop BVDV-specific memory in the presence of these antibodies.) MLV ncp vaccines should not be given to pregnant cows although some cp vaccines now carry label approval for such vaccination under certain conditions. Vaccination cannot overcome the problems caused by the presence of persistently infected animals in a herd. Thus these must be detected and removed and all introduced animals must be screened before admission.

Parainfluenza 3

Parainfluenza 3 (PI3) is a ubiquitous myxovirus that causes mild or subclinical respiratory disease in mature cattle. Its main significance lies in the fact that it predisposes cattle to infectious bovine rhinotracheitis and other respiratory diseases. Thus it is considered a part of the bovine respiratory disease complex. In practice, vaccination against PI3 is usually combined with those against other respiratory pathogens such as BHV-1, BVD, and BSRV (see Table 16.1). Inactivated vaccines are available in a great variety of combinations with other antigens. Modified live vaccines are also available as are strains attenuated for intranasal use.

Bovine respiratory syncytial virus

Bovine respiratory syncytial virus (BRSV), a pneumovirus, is the major cause of pneumonia in calves and an occasional cause of respiratory disease in nonimmune adult cows. Affected calves develop increased breathing difficulty caused by fluid accumulation in the lungs. BRSV is very common and endemic in many herds so that outbreaks typically recur every year. The disease develops around one to three months of age at a time when calves still possess maternal antibodies, and this suggests that these antibodies may not be protective. Nevertheless, pregnant cows should be vaccinated to provide some maternal immunity. Alternatively, very young animals should be vaccinated in an effort to stimulate protection by cell-mediated immune mechanisms, because helper T cell 1 responses appear to be important in conferring protection. Evidence suggests that administering an inactivated BRSV vaccine to calves in the presence of maternal antibodies may prime their T cell system and so induce partial protection. Inactivated parenteral vaccines have been difficult to assess because clinical trials have yielded equivocal results in demonstrating efficacy, and there is some evidence that they worsen the disease. Both intranasal and intramuscular modified live vaccines are also available. The intramuscular products stimulate the production of protective antibodies but may cause abortion in pregnant cows. The intranasal product can be used in pregnant animals. It can prime animals for protective immunity but the duration of this immunity is short. These vaccines are usually administered in combination with vaccines against the other major bovine respiratory pathogens.

Other important vaccines

Bovine coronavirus and rotaviruses

These viruses cause diarrhea in very young calves. As a result, they are usually controlled by a single combined vaccine that is either given to neonatal calves or to pregnant cows several weeks before calving. Two live vaccines are available for the vaccination of newborn calves. One MLV vaccine can be given orally immediately after birth. Another MLV vaccine can be administered intranasally to calves at three days. The rapid onset of immunity in calves receiving the oral or intranasal live vaccines is probably due to the production of interferon. Inactivated vaccines are also available for use in pregnant cows.

Foot-and-mouth disease

Foot-and-mouth disease (FMD) is one of the most contagious of the diseases affecting cloven-hoofed animals, and the most important disease limiting the global trade in animals and animal products. Its cause is a virus of the genus Aphthovirus of the family Picornaviridae. Infected cattle and pigs develop vesicles on their feet, nose, mouth, tongue, and mammary glands. The mouth and nose vesicles rupture and result in excessive salivation and nasal discharge. The foot lesions located around the coronary band cause lameness. In adult sheep and goats the disease may be mild or subclinical, but in juvenile lambs and kids, mortality may reach 50%. Infected animals shed large amounts of virus, and because the infectious dose is low, the virus can spread very rapidly among susceptible animals.

FMD has the potential to cause great economic losses as a result of reduced weight gain, growth failure, reductions in milk production, and loss of traction potential. About half the infected animals remain persistently infected virus carriers. There are seven known serotypes of FMDV: A, O, C, SAT1, SAT2, SAT3, and Asia-1. In addition, there are more than 60 subtypes of FMDV, and there is no universal vaccine against all of these. Infection or vaccination with one serotype does not confer protection against the other serotypes.

The United States has been free of this disease since 1929. It is also absent from Canada, New Zealand, Australia, and most of Europe. Most disease-free countries have never vaccinated their livestock. They rely on surveillance, movement controls, and controls on the importation of animal products. Sporadic outbreaks in FMDV-free countries have been controlled by the prompt slaughter and destruction of infected animals and potential contacts. In recent outbreaks, the death of very large numbers of mostly uninfected animals has led to a public outcry and questions regarding the decision to implement depopulation policies. The disease is endemic in much of the rest of the world.

All currently available FMDV vaccines are inactivated. The first vaccines originally contained formaldehyde-inactivated virus obtained from tongue lesions. Subsequently it became possible to grow the virus in cultured tongue epithelium. It is now grown in large-scale suspension cultures using baby hamster kidney (BHK21) cells. Unwanted components and tissue culture residues are removed by ultrafiltration and chromatography. When the virus reaches its maximum yield, the culture is clarified by centrifugation and/or filtration. It is then inactivated with binary ethyleneimine and concentrated by ultrafiltration. These vaccines are then adjuvanted with a mineral oil emulsion or an aqueous adjuvant such as aluminum hydroxide or saponin. Pigs respond poorly to these vaccines, and double adjuvants, such as water in oil in water, are required to generate significant immunity in this species. FMDV vaccines must undergo efficacy testing in addition to the usual identity, sterility, safety, and freedom from contamination. In endemic countries, calves should be vaccinated every six months until two years of age and then annually thereafter.

Problems with currently available FMDV vaccines include serotype dependency, limited antigenic matching between vaccine and outbreak strains, slow development of immunity, a short duration of immunity (four to six months), vaccine instability, and the high costs incurred as a result of the need for very high-containment facilities. Although the vaccines may protect against clinical disease, they cannot prevent viral persistence in the mucosa of the nasopharynx, and as a result, vaccinated animals may become asymptomatic carriers. Local injection site reactions are not uncommon with the oil adjuvanted products. Other reactions can include fever, pain, and lethargy, and also urticarial, exudative, and necrotic dermatitis. They may also induce a temporary but significant drop in milk yield.

FMD vaccines may be classified as “standard” or “higher potency” vaccines. Standard potency vaccines contain about three PD50 (protective dose 50) whereas “higher potency” vaccines contain more than 6 PD50. The latter are used to protect naïve animals in the presence of an outbreak. In countries where vaccination is practiced, vaccines are given twice a year because it is essential to maintain a high level of herd immunity. Immunity develops within seven to eight days. Because of the lack of cross-protection between serotypes and subtypes of FMDV the appropriate vaccine strain must be carefully selected if vaccination is to be effective.

Modified live vaccines against FMDV are not currently used owing to concerns about their stability and reversion to virulence. However, genetically modified live vaccines with massive gene deletions may be effective. One such example is the development of a leaderless vaccine (Chapter 4). The leader protein in this virus is nonstructural but determines virulence. Once this gene is eliminated the virus is attenuated and not transmissible, but it is both immunogenic and protective.

The antigenic determinants that induce protective immunity against FMDV are located on the virus capsid. This capsid is formed by 4 structural proteins, VP1 through VP4. VP1 is the most antigenic component of the virus. Several replication-defective adenovirus-5 vectors engineered to express FMD VP1 have been successfully tested in multiple species including swine. Such a vaccine could serve to differentiate vaccinated from naturally infected individuals. These AdV-5 vectors can only grow in cells that express the missing AdV-5 gene so they are very safe. Many other studies are underway seeking to improve on current vaccines including the use of virus-like particles, vectored recombinant, chimeric, and DNA-plasmid vaccines

The control of FMD is a national responsibility and vaccines may be used only with the permission of the appropriate national authority. FMD vaccine production facilities must operate under stringent containment and biosecurity procedures. There is obviously no need to use a vaccine in a country where the disease is not present. Nevertheless, countries must be prepared for a disease outbreak. Disease free countries have established strategic reserves of inactivated vaccines so that vaccines may be available in an emergency. For example, vaccines directed against serotypes O, A, and Asia are stockpiled in many Asian countries. The North American foot-and-mouth vaccine bank is located at the USDA Foreign Animal Disease Laboratory at Plum Island, New York. The bank stores many different serotypes of concentrated FMDV antigens in liquid nitrogen. There is no way of knowing ahead of time which serotype to vaccinate against. Once the causal serotype is identified, a process that takes about four days, these antigens can be rapidly formulated into vaccines. This would probably only occur should a FMD outbreak occur and should eradication fail to eliminate the outbreak. Because of the major economic consequences of this disease, rapid eradication remains the preferred method of control.

Emergency vaccination could play an important supporting role should a FMD outbreak occur in the United States. Currently two strategies are employed to block disease spread. Both employ vaccination of animals located in the area surrounding the disease outbreak. Once the disease is eliminated then the vaccinated animals may then be killed. This is called a “vaccinate-to- kill” strategy and may be justified by the persistence of infected carrier animals. An alternative approach would be to simply monitor the vaccinated animals closely and kill only those that show evidence of infection, a vaccinate-to-live strategy. This strategy requires the use of effective DIVA vaccines.

Lumpy skin disease

Lumpy skin disease (LSD) is a poxvirus-mediated disease of cattle, sheep, and goats. It is characterized by fever, nodules on the skin mucosa and internal organs, emaciation, lymphadenopathy, and death. LSD is endemic in Africa, the Middle East, and also southeast Europe. Attenuated strains may be used as live vaccines. Strains of capripox virus cross-react with LSDV and have been used as vaccines but they may produce severe local reactions.

Rift valley fever

Rift Valley fever (RVF) is a disease of humans in addition to sheep, cattle, and goats, and is restricted to Africa and the Arabian Peninsula. It is caused by a mosquito-borne Phlebovirus of the Bunyaviridae family. Rift Valley fever virus causes mass abortion and high neonatal mortality when it infects pregnant animals. Both live attenuated and inactivated vaccines are available for use in regions where RVF is endemic. The mouse-adapted Smithburn strain induces strong immunity within six to seven days. It should not be used in pregnant animals in which it may cause abortion or fetal malformations. Protection lasts for several years. These MLV vaccines should not be used in nonendemic countries. A formalin-inactivated vaccine is also available for use in pregnant cattle, sheep, and goats. It requires two doses, three to six months apart and annual revaccination.

Bovine ephemeral fever

This is an important arboviral disease affecting cattle, yaks, and water buffalo in East Asia and Northern Australia where it causes serious economic losses. It is caused by an Ephemerovirus. It causes a short (three-day) fever with profound depression, stiffness, and lameness. Cattle may be unable to rise. Vaccination is widely employed and both modified live and killed vaccines are available. They should be given in two doses, two to six weeks apart, well before the start of the mosquito and sand-fly season.

Mastitis vaccines

Despite the fact that bovine mastitis is among the costliest animal diseases in much of the world, there are few successful vaccines against it. One reason for this is simply anatomical. The huge volume of milk produced by modern dairy cows effectively dilutes antibodies, lymphocytes, and neutrophils. Milk immunoglobulins are poor opsonins and complement does not work well in milk. Complement will not enhance the killing of Staphylococcus aureus by milk neutrophils. The neutrophil respiratory burst requires a relatively high oxygen tension while the inflamed udder has a low oxygen tension. Milk macrophages, although abundant, are loaded with fat droplets and are less able to phagocytose bacterial pathogens than those in blood. Additionally, milk is an excellent bacterial growth medium.

The main reason, however, for this apparent vaccine failure is that mastitis itself is an expression of a cow’s innate immune response to invading pathogens. It is insufficient for any mastitis vaccine to simply promote innate and adaptive immune responses. They must in essence, be so effective that innate immune responses and inflammation are either not required or are somehow downregulated—a very difficult task indeed. Thus any vaccine that enhances a cow’s innate immune responses to a mastitis pathogen will effectively promote the disease.

Many different parameters have been used to test vaccine efficacy. These include somatic cell counts; bacterial culture; milk yield; the incidence and severity of mastitis cases; and even milk immunoglobulin (Ig)G content. Unfortunately, these parameters do not correlate well and a vaccine that shows a benefit when measured by one parameter may be totally ineffective when measured by another.

The major causal agents of bovine mastitis are either contagious, e.g., Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus dysgalactiae, or they are environmental contaminants such as Streptococcus uberis or coliform bacteria.

Staphlyococcus aureus causes subclinical intramammary infections that often become chronic. The goal of any S. aureus vaccine would be to prevent new intramammary infections, facilitate bacterial clearance and recovery, and minimize cow-to-cow transmission. In other words, enhance herd immunity. Several different S. aureus bacterins have been investigated as mastitis vaccines but most have yielded disappointing results. A bacterin that stimulates the production of antibodies against the pseudocapsule appears to be somewhat effective. This pseudocapsule interferes with the ability of milk leukocytes to phagocytose S. aureus. Antibodies induced by the vaccine thus promote opsonization and destruction of the bacteria. S. aureus vaccines designed to stimulate antibody production against its α toxin and the pseudocapsule, are also effective in some but not in all herds. Vaccines containing modified live bacteria may be more effective than killed ones.

Lysigin (Boehringer Ingelheim Vetmedica) is a vaccine consisting of a lysate of five strains of S. aureus. These are common mastitis-causing strains including phage types I, II, III, IV, and miscellaneous other groups. Preliminary experimental studies gave encouraging results because it reduced the incidence of intramammary infections, disease severity, somatic cell counts, and the development of chronic infections. The vaccine is given to heifers at six months of age, boosted two weeks later, and then boosted every six months until calving. The vaccinated cows had a 45% reduction in new S. aureus infections during the next lactation. Subsequent studies in experimentally challenged animals resulted in a milder shorter disease but cell counts remained unaffected. Other field studies have failed to show these effects. A second vaccine consists of an oil-adjuvanted S. aureus bacterin plus toxoid. Three subcutaneous doses are administered one month apart and it is only available in California. It is reported to reduce bacterial shedding, reduce California Mastitis Test scores, and reduce culling.

Other mastitis vaccines are marketed elsewhere. For example, Mastivac (Laboratorios Ovejero), is a complex combined bacterin available in Europe. It contains S. aureus, multiple streptococcal species, Escherichia coli, and Trueperella pyogenes. Little success has been reported using vaccines against Streptococcus agalactiae or S. dysgalactiae.

S. uberis vaccines containing the bacterial plasminogen activator (PauA) have shown good results in experimental studies. However, mutant strains of S. uberis lacking PauA still cause mastitis. This organism is also encapsulated and resists phagocytosis. Neutrophil influx does not correlate with protection. S. uberis is also highly variable, therefore complex strain mixtures may be required to induce immunity in different dairies. An oil-adjuvanted, S. uberis bacterin is available in the United States (Hygieia Laboratories).

Many different vaccines are available for the prevention of coliform mastitis. The J5 strain of E. coli is a mutant that expresses a lipopolysaccharide with portions of lipid A and core antigens exposed (Chapter 3). Encouraging results have been obtained by the use of a J5 mutant vaccine against coliform bacteria and against Re-17, a rough mutant of Salmonella typhimurium. Bacterins are available with different adjuvants and various methods of application. As in so many mastitis vaccine studies, successful experimental studies have not always been followed by successful field studies. However, these core antigen vaccines do provide some protection when administered during the drying-off period. They may reduce disease duration and decrease its transmissibility and also minimizing culling.

There are at least five licensed vaccines available against coliform mastitis in the United States. In general, these are given in multiple subcutaneous doses. One that is available in Europe and Canada, contains both E. coli J5 and S. aureus SP140 strain (Startvac, Hipra). As in so many cases it reduces the prevalence of S. aureus mastitis, but milk yield was reduced and it did not appear to affect the duration of disease. In other studies, the incidence of mastitis was unaffected but its severity was much reduced. One study suggested that the cost-effectiveness of using this vaccine was about 2.5:1. Other studies have failed to show this effect.

As described in Chapter 3, vaccines directed against a bacterial outer membrane siderophore receptor protein and porin proteins (SRP) block iron uptake by gram-negative enterobacteria. A vaccine containing a Klebsiella SRP appears to be very effective in reducing the prevalence and incidence of Klebsiella mastitis.

Herd-specific autogenous vaccines also been widely employed to control mastitis. Reported results are mixed, with some reporting excellent responses and protection whereas others are seemingly ineffective. Vaccination is no substitute for excellent hygiene, teat health, proper milking procedures, dry cow antibiotic therapy, and a well-considered mastitis control program.

Maternal antibodies

Prebreeding vaccinations should be completed at least four weeks before the start of breeding to ensure that maximal antibody titers coincide with the onset of pregnancy. Vaccines given to prevent losses from abortions include those directed against bacterial diseases such as vibriosis, and leptospirosis; virus diseases such as IBR and bovine viral diarrhea (BVD); and protozoa such as Neospora and Trichomoniasis. It is often also appropriate to vaccinate cows at a time when they are undergoing pregnancy testing so that antibody titers will peak at a time of greatest susceptibility.

Precalving vaccines are intended to provide colostral immunity to the newborn calf. Vaccines are given to cows to protect their newborn calves from diseases caused by rotavirus, coronavirus, E. coli, Cl. chauvoei and Cl. perfringens types C and D. As a general rule, such vaccines should be given two to four weeks before calving to ensure maximal colostral antibody titers. Vaccination against diarrheal diseases is especially important at this stage.

Preweaning vaccinations help calves handle infections associated with weaning stress. These may include Clostridial vaccines and those directed against the components of the BRD complex.

Preconditioning is the preparation of feeder calves for marketing, shipping, and admission to the feedlot. It relies on vaccination of calves two to three weeks before shipping to give time for immunity to develop. Common vaccines given to these calves include those against clostridial diseases and the viral respiratory pathogens PI3, BRSV, BHV-1, and BVD. Vaccines against Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, may also be administered. Vaccination against respiratory pathogens is standard practice in many feedlots and occurs 24 hours after arrival. It makes sense to only use vaccines against agents known to cause problems in that feedlot. A basic minimum at this stage should be a respiratory disease vaccine plus a Clostridial vaccine. Any additional vaccines should be based on known risks.

Bulls should receive the same vaccines as the cow/calf herd, excluding brucellosis and trichomoniasis. Cows and bulls should receive respiratory viral vaccines including BHV-1, BVD, PI3, and BRSV. MLV-BHV-1 may be shed in semen so this is a concern especially if the semen is to be exported. They should also get reproductive disease vaccines, including vibrio and leptospirosis, and also a 7-way clostridial vaccine. Replacement heifers under one year of age should get the same vaccines and possibly brucellosis as well.

Adverse events

Anaphylaxis (Type 1 hypersensitivity) is a potential vaccination hazard. In cattle the major shock organs are the lungs. It is characterized by profound systemic hypotension and pulmonary hypertension. The pulmonary hypertension results from constriction of the pulmonary vein and leads to pulmonary edema and severe dyspnea. The smooth muscle of the bladder and intestine contract, causing urination, defecation, and bloating. The main mediators of anaphylaxis in cattle are serotonin, kinins, and the leukotrienes. Histamine is of lesser importance.

Inadvertent intravenous administration of respiratory and clostridial vaccines in calves has been recorded as causing acute interstitial pneumonia, with multifocal pulmonary hemorrhages leading to fatal respiratory failure.

Attenuated BVD vaccines may cause problems because some are immunosuppressive. Thus they cause a reduction in lymphocyte and neutrophil numbers, neutrophil functions, and lymphocyte responses to mitogens. Some cattle are tolerant to and persistently infected with BVD. If these animals are then superinfected with another strain of BVD they may develop fatal mucosal disease. Administration of a BVD-MLV vaccine to these persistently infected animals may induce mucosal disease. Mucosal disease generally develops 7 to 20 days after vaccination in about 0.2% in vaccinated cattle.

Cattle vaccinated with a temperature-sensitive strain of BHV-1 intranasally develop latent infections. Administration of dexamethasone to these vaccinated cattle may result in shedding of the vaccine virus for up to eight days. These may be transmitted to in-contact animals. Even parenterally vaccinated calves may shed this virus transiently. It has also been reported that calves receiving MLV-BHV-1 within 48 hours after arrival at a feedlot have a higher mortality than unvaccinated calves.

Multiple vaccines administered at the same time may cause neck soreness. Gram-negative bacterins may contain sufficient endotoxins to cause a fever, anorexia, a drop in milk yield, and perhaps even abortion. Holsteins appear to be predisposed to these reactions. In general, therefore, no more than two gram-negative vaccines should be administered to an animal on the same day.

Two important vaccine-related adverse events that occur in cattle include hemolytic disease of the newborn and neonatal pancytopenia of calves. These are discussed in Chapter 10.

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Jan 21, 2021 | Posted by in GENERAL | Comments Off on Bovine vaccines
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