Immunology of the neonatal calf

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Veterinarians understand that consumption of an adequate amount of good-quality colostrum is vital to providing calves with antibodies that protect them against infectious disease during the first few months of life. It appears that other factors in colostrum are also important for helping the calf develop its own immune response to immune challenges, including vaccination.

Adequate levels of fat-soluble vitamins such as vitamin A and E are necessary for a normal immune response to vaccination or infection. “Fat-soluble vitamins such as A and E do not cross the placenta well, but they are present in high concentration of colostrum from cows that have been consuming diets sufficient in these nutrients,” says Amelia Woolums, DVM, MVSc, PhD, DACVIM, DACVM, University of Georgia. “Calves that do not ingest an adequate volume of good-quality colostrum will begin life deficient in these vitamins, which will make them unable to respond properly to vaccination as long as the deficiency persists.”

Maternal cells that are present in colostrum may also help stimulate the calf’s immune system and improve response to vaccination and other immunological stimuli. Neonatal animals of many species have been shown to absorb live maternal cells in colostrum (primarily monocytes and lymphocytes). “Research has shown that immune cells from calves receiving colostrum containing maternal cells more rapidly developed the capacity to ‘present’ antigen,” Woolums explains. “The calves’ own immune cells were more quickly able to initiate an immune response to foreign substance.” They also showed evidence of presenting antigen within a week after birth, in contrast to calves that received colostrum from which cells had been removed, which were only able to present antigen at two to three weeks after birth (AJVR 66:1854, 2005). 

Woolums notes another study showing that cells from calves receiving fresh colostrum containing maternal cells responded to stimulation with bovine viral diarrhea virus (BVDV) by 24 hours after birth (AJVR 68:778, 2007). “Although the responses to BVDV did not persist for more than a few days, they may have induced a chain reaction of immune stimulation that could have improved response to vaccination, if it had occurred,” Woolums says. These studies provide evidence that live maternal cells in colostrum can stimulate and perhaps improve a calf’s immune response if it is exposed to immunological stimuli such as vaccination or infection, although much is still not known about their effects.
 
Feeding good-quality frozen colostrum is sometimes done to provide a calf with an optimal amount if its dam’s colostrum is inadequate. However, frozen colostrum will not contain live maternal cells. “We don’t have enough information to say if it’s better for a calf to get frozen colostrum with a good level of antibody but no living cells, or fresh colostrum with a suboptimal level of antibody but live cells,” Woolums says.
 
“For now, because so much research has shown the benefit of providing calves colostrum with a good amount of antibody, it’s probably best to stick with the better-quality frozen colostrum, if that is the only way to provide a calf with colostrum containing a sufficient level of antibody. However, if fresh good-quality colostrum can be given, we now know that the live cells in the colostrum induce changes in the calf’s immune system that may lead to better response to vaccination and better pro-tection against disease.”
 
Woolums adds that other factors in colostrum such as lactoferrin may play a role in preparing the calf’s immune system to respond to vaccination or other immunologic stimuli, but more research is needed in this area.
 
Nutrition’s effect on calf immunology
Aside from fat-soluble vitamins, animals deficient in minerals such as zinc, selenium, copper and chromium have suboptimal immune responses to vaccination and other immunological stimuli. Stud-ies have evaluated the effect of supplementing diets with various vitamins and minerals to improve immunity and disease resistance in cattle. “In general, providing levels of vitamins and minerals in ex-cess of what calves require has not consistently proven to improve immune response or disease re-sistance in a clear way,” Woolums says. “However, supplementation of animals that are deficient does improve immunity and resistance to disease.”

Calves fed diets deficient in protein and energy also have suboptimal responses to vaccination and other stimulation of the immune system. “Some producers have been feeding dairy calves on ‘intensi-fied’ schedules that provide relatively more energy and protein than was historically fed to calves,” Woolums says. Research by scientists at USDA-ARS and Cornell University showed that immune cells from calves fed an intensified milk-replacer diet produced less interferon gamma and more nitric oxide in response to immunologic-stimulation than did cells from calves fed a diet lower in energy and protein (J Dairy Sci 86:3592, 2003). 

“Gamma interferon and nitric oxide are important mediators of immune responsiveness, particularly cell-mediated immune responses,” Woolums explains. “While this research showed that dietary en-ergy and protein appeared to have an effect on some aspects of the immune response, more re-search is needed before we know the importance of any effect intensified diets may have on  the re-sponse post-vaccination or infection.”

Calf stress and immune response
For young calves, such as dairy calves on a calf ranch, the stress of ongoing disease (enteric, respi-ratory or other) and suboptimal dietary energy, protein, fat-soluble vitamins or minerals are likely to be common causes of an impaired response to vaccination.

Stress is widely understood to have a negative effect on growth and disease resistance of calves, but research has shown different effects of acute or short-term stress versus chronic stress. Acute or short-term stress can actually improve immune responsiveness of animals because cortisol, epineph-rine and norepinephrine, which are released during stress, can all improve many responses of the immune system in the hours after these hormones are released, Woolums says.
 
“However, if increased levels of stress hormones are circulating for many days, immune responses can deteriorate,” Woolums adds. “Calves subjected to a brief period of stress (such as several hours) are likely to have a normal or perhaps even slightly improved response to vaccination, but calves that are subjected to stress for several days around the time of vaccination are likely to have a sub-optimal response.”
  
Chronic stress can be induced by a variety of factors including cold or heat stress, social stress associated with mixing of animals from different origins or age groups, frightening noise or other stimuli, inadequate food or water, or disease.

Vaccination in the face of maternal antibody
Research and some clinical experience in animals and humans have led to the concept that young animals with circulating, maternally derived antibody cannot be vaccinated. However, many investiga-tors have determined that young calves vaccinated in the face of maternal antibody (IFOMA) can mount an immunologic response to vaccination, and that vaccination IFOMA can protect young indi-viduals from infectious disease once maternal antibody titers have decreased to levels no longer pro-tective.

“Although vaccination IFOMA is not always successful in priming a neonate to have a protective immune response to later challenge, it has been repeatedly shown to be possible to improve the im-mune response of calves vaccinated IFOMA, if certain factors are considered when vaccination strategies are planned,” Woolums explains.

Vaccination of newborn calves cannot provide the breadth of protection against infection that good colostrum can provide and should never be considered a substitute for passive transfer of immunity provided by timely ingestion of good-quality colostrum. However, if failure of passive transfer has oc-curred, then vaccination may help calves resist disease.
 
Newborn calves can respond to vaccination if they do not have very high levels of passive antibody from colostrum, but the immune response of a young calf is not as strong or broad as the immune re-sponse of an adult animal given the same vaccine. “Moreover, neonatal calves are at risk for some infectious diseases for which we do not have good vaccines but which may be prevented by antibod-ies in colostrum,” Woolums adds. “This is why no vaccination program for neonatal calves can be considered a good substitute for the immunity provided by ingestion of good-quality colostrum.” 


Prepare the young calf for vaccination

To optimize vaccination of the young calf, Woolums suggests these steps your clients can take to make sure calves can immunologically respond.

  • Make sure the calf is on a good plane of nutrition including adequate levels of fat-soluble vitamins, minerals, protein and energy prior to and at the time of vaccination.
  • Prevent stress that goes on for several days around the time of vaccination.
  • Research suggests that calves receiving colostrum containing living maternal cells have immune responses that may be superior to those in calves that receive colostrum that does not contain living cells; so if fresh colostrum that has good levels of antibody can be given (rather than frozen colos-trum), this may improve immune responses in calves.
  • If fresh colostrum that contains good levels of antibody is not available, it’s recommend to give frozen colostrum that has a good level of antibody.
  • Evidence suggests that calves with low-to-moderate levels of maternal antibody can still respond to vaccination. Such a calf is likely to have an improved response when vaccinated later in life than if it was not vaccinated.
  • Research shows that vaccination may not be effective in calves with very high levels of maternal antibody  —  such as calves in the first month of life who received a proper amount of good-quality colostrum from a cow that was on a regular vaccination schedule.



Recommendations for vaccinating IFOMA

The exact immunologic outcome in calves vaccinated in the face of maternal antibody (IFOMA) can vary depending on many factors. Amelia Woolums, DVM, PhD, says these factors are not well char-acterized, but likely include the nature of the vaccine administered, the number of doses adminis-tered, the age of the calf, the level of maternal antibody present in the calf and the means by which a protective response is defined. Woolums says in spite of these limitations, based on currently avail-able research, some recommendations can be made:

  • Vaccination IFOMA of calves as young as 1 month of age can be successful in priming them for a protective immune response to viral respiratory pathogens at later challenge, even if challenge occurs when maternal antibodies have disappeared.
  • While a single dose of MLV viral vaccine given IFOMA to calves as young as 1 month of age can protect them from later disease, administration of two doses given IFOMA at two to four week inter-vals is preferable, if possible.
  • Vaccination of calves IFOMA at less than 1 month of age has not been as reliably protective as vaccination of calves greater than 1 month of age and, if undertaken, administration of a booster two to four weeks later is particularly recommended.
  • When calves are vaccinated IFOMA, antibody titers will typically not increase following vaccination. Thus, failure to seroconvert should not be interpreted as evidence of vaccination failure. T-cells of calves vaccinated
    IFOMA can be found to be activated within days of vaccination, and increased T-cell responsiveness may persist for weeks to months after vaccination, even if seroconversion does not occur after vaccination.
  • If calves are suspected to have incomplete passive transfer or failure of passive transfer, studies have confirmed the safety and efficacy of a single dose of many currently available MLV vaccines for common respiratory viruses (BVDV type 1 and 2, IBRV, BRSV and PI3) in seronegative calves under 1 month of age. Vaccination can sometimes protect very young seronegative calves from disease within days of vaccination. However, MLV
    vaccines have the potential to cause disease in significantly immunocompromised hosts, so a veteri-narian needs to judge the use of these products on an individual calf basis. Vaccination of sickly or malnourished calves with failure of passive transfer may be more safely undertaken the first time with a killed product, with a live product being given at a later date to provide a more broad and long-lasting immune response.
  • Although most studies of vaccination IFOMA have evaluated MLV viral vaccines, killed viral vac-cines can sometimes prime calves effectively IFOMA. The success of a killed product in this regard is likely related to the specific formulation, including the adjuvant.

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