Using vaccines to improve Mother Nature’s plan for immunity in cattle by: John A. Ellis, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

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Cattle, humans and other animals are born into a dirty world – a world filled with “germs,” viruses, bacteria, and other microorganisms – many of which cause disease. Many of these microorganisms are endemic – or always there in the animal populations they infect. So, how does Mother Nature protect animals from infectious disease and how can we learn from what she does and improve on Mother Nature’s “program” with vaccines? That is the subject of this brief review.

Protection from disease is a multi-step immunological process. The first step is one that all successful dairypersons are very familiar with, even if they don’t think about it very much; it’s become a matter of course. Colostrum management is a first essential step in protecting young cattle from infectious disease and establishing a foundation for immune responses later in life. Today, virtually all dairypersons know that a calf should receive about 2 liters of high-quality colostrum as soon as possible after birth – and certainly before 12 hours of age. This can be in the form of maternal colostrum or a high-quality colostrum replacement product that is high in antibodies or “immunoglobulins,” as immunologists call them. Immunoglobulin (Ig) G1 is the most important antibody in colostrum. The timely use of vaccines in the cow can increase the amount and quality of IgG1 in the colostrum. Immunoglobulin, and other constituents in colostrum, are absorbed directly through the cell lining of the calf’s intestinal tract. But, timing is of the essence in colostrum delivery, since this transport process gradually slows down and stops altogether by about 24 hours after birth. Overall, this process is called “passive” immunization, because the calf is the passive recipient of the components of immunity, primarily the immunoglobulin. As with most things in biology, passive immunity is rarely an “all or none” phenomenon, but rather a sliding scale or bell curve, unless the calf receives no colostrum at all. Therefore, the duration of passive immunity is variable and mostly dependent on the amount of IgG1 that is absorbed from the colostrum. Good husbandry of the calf can enhance the absorption process. Nevertheless, usually, by about 2 months of age effective passive immunity will have disappeared, because absorbed antibodies decay as a normal physiological process. So, how come most calves don’t die of infectious diseases at that point?

The second part of Mother Nature’s plan for protecting populations from dying in massive numbers from infectious disease is maybe not as obvious as the importance of colostrum to most people. It actually involves the natural exposure of young animals to germs, both in the environment and those shed from immune adults in the population who can be infected by various germs but not get sick. And, of course, the reason why this exposure to germs doesn’t sicken or kill most young calves or other babies is the protective effect of maternal antibodies that have been absorbed and can effectively neutralize or kill pathogens. This process of exposure to germs in the presence of maternal antibodies, in effect, is an important first “free vaccination” for the calf. This natural exposure that, importantly, occurs at mucosal surfaces, in other words, the lining of the respiratory and gastrointestinal tracts, effectively “overrides” maternal antibodies and results in “priming” of the calf’s immune system. This is a necessary first step in the development of “active” or “adaptive” immunity in calves and other neonatal animals.

Once a young animal has been effectively primed, the third part of Mother Nature’s plan comes into play – boosting the primary responses. Boosting, or effectively strengthening, a single primary exposure is necessary because young immune systems are not mature and just one exposure usually doesn’t result in a long-lasting immune response. As mentioned, most of the important infections in human and other animal populations, historically, have been endemic or always there. Moreover, what most people perhaps don’t realize is that immunity is rarely complete or “sterilizing.” Instead, what usually happens is that exposed individuals develop “clinical immunity” that prevents or reduces disease but does not completely prevent infection or “shedding” of germs in nasal secretions or feces, depending on the germ. What this means is that normal day-today interactions that occur in herds of cattle, humans, cats, or crocodiles provide opportunities for boosting primed responses. Overall, this process contributes to “herd immunity” or immunity in the population overall.

Admittedly, this story of “free vaccination” may sound like some sort of happy-ending academic fairy tale. But, there are numerous epidemiologic data, or examples from populations, that make this story a reality. Things are usually best appreciated in their absence. One of the best examples of what happens when this process of natural vaccination doesn’t happen is the history of the Western Hemisphere. Many important human germs, such as smallpox and measles, were endemic in Europe for centuries before vaccines were available. Exposure to them resulted in herd immunity for those pathogens. In other words, there was reduced disease in the face of natural exposure. These germs, and others, were not endemic in indigenous populations in the “New World”. So, when clinically immune European settlers came and exposed indigenous people to their germs, the native Americans, who had no protective immunity, died in massive numbers and the rest is history.

But, what moves all of this beyond a history lesson to a place where its application results in more rational use of the tools we have available, and, importantly, in improved health in cattle? Certainly, cattle and other animals survived for eons without humans or vaccines. So, how can we learn from the natural history of infectious diseases and improve on Mother Nature, or at least, hopefully, better manage infectious diseases? In summary, perhaps consider these three practical applications – both the obvious, and, maybe, the not so obvious:

First, pay attention to colostrum management! This is obviously not a new concept. But, without optimal passive immunization, subsequent vaccination will most often be futile – a waste of money – because the calf will either succumb to E. coli diarrhea or be too unhealthy to respond most effectively to vaccines. Remember, colostrum quality can be improved with timely vaccination of cows, with modifiedlive vaccines prior to breeding, or with inactivated vaccines three weeks prior to calving, depending on management systems.

Prime calves (and other animals) early in life (as early as day 1) with mucosally delivered vaccines – intranasal or oral. Effective, combination intranasal vaccines are available for important respiratory pathogens in calves, including bovine respiratory syncytial virus and parainfluenza-3 virus. The use of intranasal vaccines containing temperature-sensitive bovine herpesvirus is preferable for safety concerns. Oral vaccines for bovine coronavirus (and rota-virus), which cause both enteric and respiratory disease in calves, are probably most effective if administered intranasally; some will be swallowed and some will more effectively expose the respiratory tract. Traditional approaches aside, do NOT use injectable vaccines in passively immune animals and expect to get much priming of the immune system. Just as maternal antibodies protect, they effectively block most effective priming of immune responses.

Boost primed responses with injectable vaccines. This can be done at about 2 months of age when maternal antibodies will have substantially decayed. Waiting until weaning (about 6 months of age, at least in beef cattle) is unlikely to result in effective boosting of neonatally primed responses, as they will generally be short lived. The choice of vaccines to most effectively achieve boosting will vary with the pathogen. Stay tuned for additional applied studies that address this issue.

At a time when there is increasing concern about the use of antibiotics in food animals, and, relatedly, the development of resistance to antibiotics in both humans and veterinary patients, more timely and judicious use of vaccines, will not only improve calf health but also address consumer concerns about “food safety.”

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