Vaccination Programs for Calves
ACVIM 2008
Geof W. Smith, DVM, PhD, DACVIM
Raleigh, NC, USA

The field of neonatal immunology and calf vaccination is going through a revolution in veterinary medicine. Therefore opinions on when and what to vaccinate calves for will vary widely amongst experts. It's very likely that what may be effective and/or economical for one herd may not work for another. The purpose of this talk will be to give an overview of routine vaccination recommendations in both beef and dairy cattle. The focus will be on vaccination strategies to limit diarrhea and respiratory disease in calves.

Neonatal Immunology

A common misconception is that calves are born without a functional immune system. Actually all parts of the immune system develop during gestation. For example, the thymus reaches its maximum size during mid-gestation, thymocytes differentiate into specific CD cell lines, B cells develop and differentiate in fetal bone marrow, etc. When the calf is born, its immune system is fully developed but very immature or unprimed. Therefore, although the immune system is present at birth, it's unable to respond to most antigens.

The immune system will slowly develop and will be in full working order somewhere around sexual maturity (8-10 months). Calves are born with only about 12-50% of adult complement levels which take about 6 months to fully develop. Numbers of phagocytic cells are higher in the neonate than in an adult, however the function of these cells is very poor (neutrophils reach adult function about 4 months of age). T cells (CD4, CD8) cells reach peak levels at about 8 months of age and B cells somewhere around 5-6 months. So although calves can indeed respond to antigens, this response is much slower and weaker than in an adult animal. Therefore they are more susceptible to disease.

Another misconception is that the presence of colostral or maternal antibody will always block the immune response to vaccination. This "interference from maternal antibody" concept comes from research that has measured the response to vaccination only by analyzing antibody titers. These studies have shown that if maternal antibody levels are high, they will likely not be much higher after vaccination. However recent studies have shown the formation of B cell memory responses and cell mediated immune responses in the face of maternal antibody. Therefore we have come to realize that the efficacy of vaccination can't be measured strictly by following antibody production or documenting increases in titers. Rather the specific antigen and presentation of that antigen becomes important, as protection from some diseases can be achieved with vaccination in the neonatal period while for other diseases there will be no benefit.

Protection against disease is often primarily dependent on one type of immunity--either cell mediated (T cell) or humoral (B cell). Therefore for diseases which cell mediated immunity is the primary source of protection (i.e., IBR, BRSV, PI3, and intracellular bacteria like Mycoplasma, and Salmonella) you could expect to see some protection from vaccination neonatal calves. Not because the vaccine was able to boost titers or antibody levels, however the vaccine was able to stimulate the cell-mediated immune system. Thus the T cells now "primed" and are better able to respond that antigen or specific disease. However for diseases in which protection primarily comes from antibodies (BVD, Pasteurella, E. coli, rotavirus, etc) you would not expect to gain any significant protection from vaccinating calves and must instead count on protection from specific colostral antibodies.

Vaccinating to Prevent Calf Diarrhea

Although there is very little published science in this area, in my opinion every pregnant cow should be given a killed rotavirus/coronavirus vaccine containing a K99 E. coli toxoid prior to calving. These products include Pfizer's ScourGuard 3® (K)/C, Scour Bos® 9 from Novartis, Scour Vac® 3K+C from Durvet, Scour Vac® 9 from AgriLabs, or Schering-Plough's Guardian® vaccine. All of these products are designed to be administered prior to calving and will boost colostral antibody titers to these enteric pathogens. Although this certainly does not guarantee complete protection from diarrhea, colostral antibodies have been shown to be the most effective way of producing immunity for these pathogens. Colostral antibodies provide local (mucosal) protection in the small intestine and absorbed serum IgG1 can be re-secreted from blood back across mucosal surfaces for an extended period of time to help prevent enteric diseases.

There is very little published data available on oral vaccines that are designed to be given to calves at birth to boost immunity to enterotoxigenic E. coli, rotavirus and/or coronavirus. Products containing monoclonal antibodies specific for E. coli K99 pilus antigen can be very effecting in preventing diarrhea from enterotoxigenic E. coli. These products include Bovine Ecolizer® from Novartis, Bar-Guard-99® from Boehringer Ingelheim, Cattle-Vac® E. coli from Durvet, Colimune®-Oral from Bioniche, and E-Colicin-B® from AgriLabs. In the face of an enterotoxigenic E. coli problem in a herd that has not received colostrum from cows vaccinated against E. coli as discussed above, these products can be used successfully to prevent infection. The K99 antibodies provide local immunity in the intestines to directly block the binding of E. coli bacteria to enterocytes. The immunity is short-lived, however since enterotoxigenic E. coli is generally only a disease of very young (1-3 day old) calves, this short-lived immunity is generally protective. However these products are not needed if the dam has received a vaccine during the dry period as discussed above and generally are recommended only for "emergency" control during outbreaks.

Other oral vaccines such as First Defense® and Calf-Guard® are intended to be given to calves immediately following birth to prevent diarrhea caused by rotavirus and/or coronavirus. Several field studies using these products have shown them to be ineffective in controlling calf diarrhea due to either virus on farms. In challenge studies, oral vaccines did offer some protection against viral diarrhea when given to specific pathogen free (colostrum deprived) calves. However when the vaccine was given to calves that also got colostrum, it failed to offer any protection against the development of diarrhea. These studies demonstrated that the vaccine virus present in these products is inactivated by antibodies in the colostrum causing failure of these products under most field conditions. I do not recommend using oral vaccines to prevent rotavirus or coronavirus diarrhea in calves and believe vaccination of the dry cow and ingestion of colostral antibodies to be a much better approach. However if you decide to use an oral rota/coronavirus vaccine in calves, it must be given at least 30 minutes prior to any colostrum administration (nursing).

Vaccinating to Prevent Respiratory Disease

In the beef industry the recommendations are generally to vaccinate calves with a product containing modified-live BHV-1, PI3, and BRSV around 5 months of age with a follow-up booster 3-4 weeks later. If the calves have been weaned or if it can be used safely (according to label approval) in calves nursing pregnant cows, I also recommending using a vaccine containing modified-live BVD virus. Ideally, both vaccinations should be completed 3 to 4 weeks prior to shipping calves to afford maximum protection against respiratory disease.

The optimal timing of vaccination to prevent respiratory disease in dairy heifers is somewhat more complicated. Since "enzootic pneumonia" of dairy calves generally occurs at a younger age than "shipping fever" pneumonia of beef calves, it would be ideal to have immunity at a much younger age. However the degree to which neonatal calves respond to vaccination is controversial. For some diseases protective levels of maternal antibody hang around for quite awhile. For example BVD titers >1:16 are generally considered protective against the development of severe clinical disease (due to BVD) in cattle. Calves that receive colostrum usually have titers >1:32 for 3-4 months. Therefore it has been shown that calves don't really become susceptible to BVD infection until 4-5 months of age and thus a traditional vaccination timeframe similar to that used in the beef industry would be appropriate.

However for other viral causes of pneumonia such as BHV-1 and BRSV, maternal antibody disappears much faster (2-4 weeks) and calves are susceptible at a younger age. Therefore there has been considerable interest in vaccinating newborn dairy calves for respiratory pathogens. As discussed above, we generally don't see a big "antibody" response after vaccinating young calves however we still may have protection from priming the cell mediated part of the immune system. BHV-1 and BRSV are both diseases in which the cell-mediated immune system offers the primary source of protection against disease. Therefore it has been suggested that vaccinating young calves could produce some protective immunity against respiratory disease.

Although published field trials demonstrating that vaccinating young dairy calves is effective and economical, it is commonly done on many farms. To use these vaccines optimally, it is recommended to give an initial dose at 1 week of age with a booster at 5 weeks of age. Calves in general will not respond to a modified live bacterin within the first 5 days of life. Although the exact reason for this is not well understood, it is thought to correlate with the T-cell compartmentalization associated with the calving process. In unpublished clinical trials, there is little immunologic response to viral respiratory pathogens when vaccines are administered during the 3-5 week window in calves. Again the reason for this is unknown but it corresponds with the disappearance of maternal T cells from the calves. However by 5 weeks of age, the calf's T cells have matured to the point where they can respond to vaccination. I am not a proponent of vaccinating young dairy calves in every situation and in most small, closed herds it is likely not economical. However in large dairies where calves have significant exposure to respiratory pathogens, the use of a vaccine containing modified live BHV-1, PI3, and BRSV at 1 week and 5 weeks of age might be economical.

Another approach to consider is the use of intranasal vaccines in young calves. They induce primarily local (mucosal) immunity as opposed to systemic immunity. Although they have a short duration of protection, they can be used effectively to prevent respiratory disease in young calves. I do not recommend systemic vaccination in dairy calves that are (or will be) stressed due to shipping as they are not likely to respond and vaccination can be viewed as just another stress that will decrease their resistance to disease. However intranasal vaccines will work much better in these calves as local (mucosal) immunity and response to intranasal vaccination is not affected by stress. Intranasal vaccines can be given at birth and repeated at as needed to boost immunity 7-10 days prior to anticipated or historical periods of respiratory disease (should be separated by at least 2 week intervals).

The use of bacterins to control Pasteurella multocida and/or Mannheimia hemolytica is not recommended in calves. Protection against these pathogens is primarily controlled by the humoral immune system. Since young calves are not able to elicit a strong antibody response to vaccination, they would be very unlikely to benefit from these bacterins. This has been confirmed in field trials where Pasteurella and/or Mannheimia bacterins have not been effective.

Vaccination to Prevent Leptospirosis

There is more and more interest in vaccinating cattle at young ages to prevent renal colonization by the leptospiral serovar hardjo. Immunity to Leptospira has been shown to be serovar specific and most of the historical polyvalent vaccines provide good protection against all serovars except L. hardjo. However they do not prevent renal infection, urinary shedding, or fetal infection by this serovar. Only Spirovac® (from Pfizer) and Leptavoid® (Schering-Plough) have been demonstrated to provide good protection against L. hardjo. In beef calves, it is recommended to vaccinate for L. hardjo the first time they are handled (typically at 3 to 5 months of age), with a booster 4 to 6 weeks later. In dairy calves, the recommendation is to vaccinate much younger. The initial dose should be given at least a couple of weeks before the calves leave the hutch (4 to 5 weeks of age) with a booster 4 to 6 weeks later. Spirovac® is approved for use in calves 4 weeks of age or older and this early immunity allows protection against L. hardjo before calves are commingled. Data from unpublished field studies show a full one-year of protection from L. hardjo in ocular challenge studies even when calves are vaccinated at 4-5 weeks of age.

Vaccination to Prevent Salmonellosis

I often get questions about the optimal vaccination regimen to produce protection from Salmonella in young dairy calves. The answer to this question is complex because immunity to different Salmonella serotypes appears to be quite different. The most important component to Salmonella control is to limit exposure. If you reduce the number of bacteria the calf is challenged with by controlling management factors, you will decrease disease and mortality rates. Calves under a year of age do not respond well to killed Salmonella vaccines and need live bacterins. Entervene®-d is a modified live S. dublin vaccine from Fort Dodge that is approved for use in healthy calves over 2 weeks of age. This vaccine also has some cross protection against S. typhimurium as the B and D serogroups have antigenic similarities. This vaccine has also been used in an extra-label manner in newborn calves to protect against Salmonella mortality occurring around 5-10 days of age. Although it can be effective in this manner, some producers have reported adverse reactions to vaccination in newborn calves. Another possible approach is to vaccinate with Endovac-Bovi® from Immvac. This is a toxoid derived from S. typhimurium that is designed primarily to decrease the clinical signs associated with acute Salmonellosis. This product is approved for use in adult cattle to lessen the clinical signs of coliform mastitis. However some practitioners have tried to use this in young calves to decrease the severity of Salmonella with mixed results. Controlled clinical trials are indicated to determine whether or not this approach would offer any significant protection.

Speaker Information
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Geof Smith, DVM, PhD, DACVIM
North Carolina State University
Raleigh, NC

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