8 ways to boost immunity in livestock, By Victor Cortese, DVM, PhD, Dipl. ABVP – Owner of Cortese Veterinary Consulting, LLC

Maintaining a robust and well-functioning immune system in animals is critical for animal health and well-being. Dr. Victor Cortese, veterinary immunologist and consultant, discusses eight essential strategies for boosting the immune system, including the often-overlooked aspects of vaccine dosage, quality assurance, and interpretation of antibody titers. His insights offer a holistic perspective on preserving animal health and productivity.

1. Treat the immune system well

One goal with the immune system is to keep it from working too hard, Victor Cortese, DVM, PhD, says, because an animal requires more energy and protein if the immune system is challenged. When that production cost occurs, it can have long-term impacts.

“If you’re over-vaccinating pigs in the first 30 days of life, it can have a long-term negative impact on weight gain, feed efficiency and reproductive capabilities, yet we have tended to think this is the best time to vaccinate. As we learn more about perinatal programming, this is an area in which we need to be careful.” Cortese says. Not all animals respond to vaccination in the same way. Cortese reminds swine veterinarians that there are at least a dozen factors that could affect the ability of an individual animal to respond to vaccination, including:

1. Type of vaccine
2. Proper handling of vaccine
3. Fever
4. Subclinical disease
5. Parasites
6. Maternal antibodies
7. Heat (external temperature)
8. Stress (higher levels of cortisol)
9. Nutrition status (especially micro-minerals)
10. Current immune status
11. Prior pathogen exposure or vaccination
12. Use of antibiotics (especially with live-bacterial vaccines)

2. Check nutrient availability

An animal’s immune system depends on the available nutrients it receives, and this should be checked frequently.

Cortese recalls that when a manufacturing facility producing vitamin A had to close because of a fire, the vitamin was sourced from other countries where variability was greater. Pigs and cattle across the US began to show signs of vitamin A deficiencies.

An Iowa swine veterinarian contacted Cortese at that time and said he couldn’t get pneumonia under control in a barn. Cortese suggested he pull some blood from the pigs, and when he did, Iowa State University diagnosticians told him it was the lowest vitamin A levels they’d ever seen in pigs.

“What the pig is absorbing is what’s useable in the ration,” he reminds veterinarians. “We can’t assume anymore, particularly as our facilities get bigger, that what’s been balanced on paper is what a pig is absorbing. It’s important to periodically check trace-mineral and vitamin levels to understand what’s being absorbed and the impact nutrition has on the immune system.”

Water interactions are also a factor, he says. “I have customers with wells in Indiana right now that are so high in zinc that they’re causing zinc toxicity. We need to do a better job of checking.”

3. Consider heterologous prime-boost

Heterologous prime-boost vaccination programs can be quite beneficial in developing a more robust immune response. This is well-documented in cattle^1,2 and is starting to be explored in swine as well.³ Heterologous prime-boost, by definition, involves priming the immune system to a target antigen delivered by one vector, route or mechanism, and then selectively boosting this immunity by re-administering the antigen in the context of a second and distinct method,⁴ Cortese explains. It is also used extensively in poultry.

“Research in humans has also highlighted the power of prime-boost strategies in eliciting protective cell-mediated immunity and subsequent efficacy,”⁵ Cortese says.

Over the past decade, studies with cattle have shown that heterologous prime-boost immunizations can be performed by: (1) using the same antigen and administered via different routes of administration, or (2) presenting antigens from the same bacteria or virus in a different manner. More recent heterologous prime-boost studies combine two different antigen presentations and routes of administration to determine maximum immune responses and protection to various pathogens.^1,2 These studies have shown that the use of heterologous boosting can not only improve the immune response but increase the degree and/or duration of protection provided over traditional homologous boosting.

“To me, the most interesting and unexpected finding is that, in many cases, heterologous prime-boost is more effective than the homologous prime-boost approach,”⁶ he says, adding that the rapid progress of novel vaccination approaches, such as DNA vaccines and viral vector-based vaccines, has further expanded the scope of heterologous prime-boost vaccination.⁷

“There are enough papers published now that heterologous prime-boost is a commonly accepted immunologic concept,” Cortese says, adding that “greater levels of immunity are often established by heterologous prime-boost than can be attained by a single vaccine administration or traditional homologous boost strategies.”

“Where permissible, heterologous prime-boost is a sound health strategy that needs to be further explored in all species, especially when traditional approaches fall short of expectations.”

4. Know the effects of cytokines, lymphokines

Cytokines and lymphokines have multiple roles in the immune pathways, so it’s important to understand their primary and secondary effects, Cortese says. For example, if a veterinarian is using an antiviral, does it downgrade the antibacterial that’s being used at the same time? “You have to know all the effects of that cytokine and lymphokine. The range, or the dosage, between effectiveness and toxicity is very narrow,” he says. “We can do this with the way we vaccinate animals. We can cause the over-release of cytokines with the number of antigens, and it can impact feed intake and increase mortality.”

5. Consider MHC (major histocompatibility complex) when vaccinating

According to Cortese, humans share a common MHC in only one out of every 350,000 to 500,000 people. MHC is a group of genes that code for proteins found on the surfaces of cells, including killer T cells, that help them recognize foreign substances. In pigs, the MHCs are much more closely related, so there isn’t as much variation. “In the past — 10 or 15 years ago — the belief was that a piglet was born with this blank slate, waiting for colostrum so we could start vaccination,” Cortese says. “The belief now is that pigs are born with very small numbers of killer T cells, and vaccination causes a form of expansion to protective levels.”

6. Don’t get hung up on titers

Veterinarians can spend time looking too closely at antibodies on enzyme-linked immunosorbent assay, or ELISA, Cortese says. “ELISA basically measure all the antibodies to an antigen, protective or not,” he says. “Scientists can develop a vaccine that will give you a very high level of those titers, but those titers can block protective antibodies from actually neutralizing an antigen. The trend is to over-interpret titers.”

As an example, he pointed to a study that looked at three different vaccines for a cattle disease.⁸ The group that had the highest titer gave the lowest protection while the group that had the lowest titer had the highest level of protection. “A titer tells you whether an animal was exposed to either a vaccine or an infection. Be very careful correlating titers to level of protection,” Cortese said.

7. Avoid partial dosing

Partial dosing is another area in which Cortese is concerned. “You may be losing both antibody and cell-mediated immunity if you partial-dose,” he says.

There’s another fallacy to partial dosing. When a vaccine is released for distribution, it has an expiration date. “We determine the minimum immunizing dose needed to induce a protective immune response. Then we may increase potency of the vaccine such that we can still meet the minimum immunizing dose at the expiration date,” Cortese says.

“If you partial-dose a vaccine, you’re never giving the same dose. The only time I know that I’m above the minimum immunizing dose required to induce a protective immune response, is when I give a full dose, because that is what was required by the USDA to assure that the label dose will provide a minimum immunizing dose through the expiration date,” he explains.

8. Safeguard vaccine quality

Vaccines will degrade over time, Cortese said, including ready-to-use vaccines.

“Producers and veterinarians should conduct comprehensive vaccine audits periodically,” Cortese said. “These audits don’t start with how vaccines are administered. They should start in the supply room first, where vaccines arrive and are stored.”

If the refrigerator isn’t set up at the right temperature, every dose from the stored vaccines could be compromised. Cortese has seen facilities experience significant losses simply because their vaccines were mishandled as a result of refrigerators being out of spec.

New outlook on immunology

There’s no question that researchers’ knowledge of the immune system and how it responds to infection, as well as vaccination, has changed dramatically. As a result, new strategies to better control disease are continually being researched and identified.