Like porcine reproductive and respiratory syndrome virus, swine influenza virus is a dynamic RNA agent that continually evolves, facilitating an ever-changing antigenic interface with the host’s immune response. In simple terms, the virus goes incognito.

This ability to change freely is an accident of nature that has likely existed among viruses since life began. RNA viruses probably were among the first viral agents to torment living hosts. 

Moreover, SIV, like PRRS, has multiple mechanisms that allow for rapid and continuous random change. The battle between living host and non-living virus never ceases because extinction is the outcome if either fail to produce an adequate response.

That’s the backdrop that scientists and vaccine producers face when attempting to develop an effective RNA vaccine. In contrast, DNA viruses tend to be more stable and change genetic code slowly. DNA viruses typically maintain existence by other mechanisms rather than depending on vigorous evolution. That’s why DNA viruses are good vaccine candidates. RNA viruses simply change, avoiding the vaccine’s immune response.

This paradigm doesn’t always hold up, but there are some compelling DNA-virus examples. Porcine circovirus type II vaccines have been shockingly effective. Pseudorabies is another example, as the vaccine essentially eradicated that disease. In simple terms, RNA viruses are a challenge for vaccine makers, often failing to provide year-over-year success.

A Little History

It appears that SIV entered pig populations during or shortly after the 1918/1919 global human-flu pandemic. This virus, designated H1N1, adapted to the pig and remained stable for more than 80 years. No one understands why it remained alone for so long, but once other strains entered our pigs there’s been no abatement.

Many veterinarians have dendograms (family trees) of SIV isolates that rival those of PRRS. Even in the same production flow, many different isolates may exist. There are three major influenza subtypes circulating in U.S. pig populations, based on the major surface antigens — H1N1, H1N2, and H3N2.  Other surface types have been recognized (H3N1, H2N3, etc….), but they’ve not been as successful.

Of course, it’s not that simple; within a major group there are multiple variant subtypes called clades. Vaccines produced from a certain clade may provide little cross protection against other clades and none between major surface types. 

Vaccine production is a near static endeavor while virus survival in a host is dynamic. Keeping up with virus change and new subtype introductions in a large pig production system is nearly impossible. Most recent evidence shows viruses circulating in the U.S. swine herd have genetic code from avian influenza viruses that make them better adapted to pigs. There’s additional evidence that human influenza viruses may also share genetic codes with pig viruses. Human-to-pig flu transmission may be a common route of new virus codes into swine influenza isolates along with avian and other pig sources.  

There are some recently discovered problems associated with killed-flu vaccines. Beyond the failure of cross protection is the apparent enhancement of pathology (severity) in some vaccinated pigs. National AnimalDiseaseCenter researchers have demonstrated that piglets vaccinated with killed vaccines, then challenged with a virus from another genetic clade within the same subtype, suffer greater disease than unvaccinated but challenged controls. The exact mechanism is not fully understood; a hypothesis is that non-neutralizing antibodies help the virus enter susceptible cells. 

The researchers also found modified-live vaccines or natural exposure to flu virus will produce demonstrable cross protection between subtypes, avoiding the enhancement and vaccine-failure issues. 

Opinion and Recommendations

So, here’s the opinion part of this article; it will be subject to ridicule and conjecture, but I look forward to the debates.

Flu vaccination in sows may be counter productive in many cases. If a sow herd experiences a natural exposure to influenza (show me the ones that do not), that herd will develop natural immune protection. Because it was exposed to a live virus, it will have cross protection against the next natural exposure. Using a killed-vaccine that is antigenically different from circulating viruses could, and in my experience often does, upset the apple cart. Large sow herds that use killed vaccines continuously in the adults sometimes develop influenza issues in nursing pigs.

That’s likely due to the same enhancement phenomena as with vaccinated piglets in NADC’s studies. Sows stimulated by vaccination make antibodies against the vaccine strains, blocking an antibody response to the circulating virus. Immunity is far more complex than making a few antibodies; although in the case of SIV, specific neutralizing antibodies are protective. When the vaccine and farm virus are different and the antibodies don’t cross-protect, allowing the farm virus to infect the nursing pigs.

Think about it; nursing pigs are the only susceptible animals on the farm, and they’re only susceptible if they don’t receive the correct colostral antibodies. In this case, the SIV sow vaccination may be responsible. 

There are ways around this. Using quality autogenous flu vaccines that match the virus affecting the nursing pig is one answer. A word of caution; when using multiple viruses in an autogenous vaccine, it’s important to assess the post-vaccination antibody response. That’s because H3N2 viruses often block a H1N1 response when they’re in the same bottle.  The commercial vaccines have overcome this problem. Unless the response is measured, you may waste time and money adding a H1N1 to an autogenous H3N2 vaccine. Even so, sow herd SIV vaccination is questionable other than for short-term and only for specific situations, targeting a specified virus as described above. 

Requiring annual influenza vaccinations for employees is a sensible approach since there’s evidence that some new viruses entering the pig populations originate from people. Some systems that have taken this approach report greater SIV stability. 

The greatest value-creation opportunity for influenza vaccines is in the growing pig. Again, matching viruses is essential for success as cross protection between subtypes with killed vaccines is minimal at best and may do harm. It’s critical that isolates be typed and sequenced in large systems before adding them to a vaccine or using a commercial product. Antibody response to all the components in multivalent vaccines should be demonstrated in vaccinated pigs. Hopefully, the biologic companies will soon respond with modified-live or other more technical solutions to current killed-vaccine issues. Horses receive modified-live influenza vaccines, so the model is not new. 

Designing a vaccination protocol for any production system requires diagnostic diligence. The veterinarian needs to know what surface antigens are involved. Then the virus clade for H1s must be determined. When using a commercial product matching clades is essential. If the diagnostic lab cannot type a virus then commercial vaccine is more likely to cause harm than provide solutions. Matching the H3N2 also is important even though today there’s only one dominant circulating cluster. While the “classic” flu virus is still around, it’s rarely recovered. 

Other common-sense practices that may prevent new virus entry is to implement exclusionary biosecurity. Bird-proofing barns and using municipal-quality water is essential. Surface water is especially risky. On-farm water treatment programs are often neglected, creating opportunity for influenza virus entry. 

Preventing human-to-pig-to-human exposure requires routine dust mask use, hand washing between rooms, showers and designated farm clothing. Using disposable gloves between litters can help, too. Instructing farm personnel to stay at home when they have flu symptoms is wise, but it can create staffing challenges. Isolate incoming replacement stock for at least 30 days.

Production scale certainly influences influenza mutation or what scientists refer to as antigenic drift. The more pigs a virus can infect and the longer it takes to go through a population, the more likely the virus will become endemic through gradual but continuous change. SIV is no longer a seasonal (winter) disease occurrence. 

The bottom line, influenza control is far more complicated than grabbing a vaccine bottle. It takes a continuous search for and understanding of new virus types, flexibility in vaccine production and a careful match between vaccine virus and circulating field virus. Perhaps in the near future we will have new technology to help us in the battle.