President’s message: Influenza – the doleful footprint of vaccines

Butch Baker, DVM

Over the course of the H1N1 pandemic, scions of information and misinformation arose as from the ashes of the phoenix – or should we say the ashes of the swine industry. Thankfully there is still a flame, although somewhat flickering where once coruscate. All are aware of the economic woes precipitated by heavy-handed use of “Swine Flu” by the media and critics of modern sustainable pork production. But this editorial is not about that issue. This message is about influenza vaccines – how should they be logically applied for the benefit of the pig, people, and our industry? Interestingly, most vaccine used in the United States is autogenous, a significant shift from earlier times when licensed commercial influenza vaccines ruled. What accounts for this transition? Is it progress or a reaction to repeated vaccine disappointment? Even our human medical counterparts have suffered paramount vaccine supply and efficacy issues. Is there any cure for our influenza vaccine anguish?

It is generally ascribed that influenza antigenic drift is perpetuated by immune pressure. Without vaccine intervention, this pressure remained minimal in past decades, primarily generated in the growing-pig populations rather than the much smaller and naturally immune adult populations. This natural immunological model functioned well for pig and virus for 80 years following the introduction of the H1N1 Spanish flu into pigs amid the 1918 pandemic. Over time, the species-adapted virus had little impact on our breeding animals, since the majority of selects endured exposure from seasonal H1N1 circulation each preceding fall and winter. Natural exposure promotes greater cross-protection, further reducing drift and perhaps preventing successful divergent introductions. It was an era where batch farrowing and internal selection of the next generations ruled. Commingling of growing pigs was at a minimum. The hemagglutinin (HA) gene evolved slowly, acting with an inapparent booster effect on the North American breeding herds while the growing pigs bore the bulk of clinical signs. Because HA neutralization is an essential component of an effective immune response and the main driver of HA evolution, relative antigenic stability was maintained. Having a seasonal renewal of naive populations to infect, no impelling demand for drift occurred. The cycle reoccurred each fall-winter-spring season. Amazingly, no successful North American heterologous introductions occurred until 1988, when human H3N2 entered the Canadian industry. During the late 90s, a triple reassortment H3N2 appeared in the United States – the root of our current conundrums. The old patterns have been superseded by rapid gene reassortment and replacement. This breakneck evolution of HA through drift and shift has obviated competent vaccination with existing vaccines, thus the need for transparent and systematic national surveillance and adoption of new vaccine technologies and strategies.

We might argue that all-in, all-out multi-site production should slow antigenic drift; however, additional forces are at play. Recent studies indicate that virus movement between previously exposed and naive populations accelerates drift. This easily occurs in the continuously produced growing-pig populations. Likewise, in human medicine, it is thought that unvaccinated and naive juveniles fuel accelerated drift.

Those of us familiar with the past recall how infrequently adult-herd influenza outbreaks occurred prior to the mid-90s. With the advent of H3N2 this abruptly changed, perpetuating an apparent need for adult vaccination. The bio-companies responded, but in the words of Bob Dylan, “The times they are a-changing.” Today, H3N2 rarely afflicts Midwest pigs. It has been replaced by the triple reassortments H1N1 and H1N2. So how should we cope with this seemingly unlimited viral predestination and what crystal ball holds a glimpse of future vaccination strategies? Our best strategy may be to vaccinate all growing pigs with HA antigen highly matched to circulating influenza strains.

Current research also illustrates the need for close HA matching in killed vaccines because of the yet unexplained immunological phenomena leading to pathological enhancement. Killed vaccines and perhaps mismatched colostral antibodies often enhance mortality and morbidity in growing pigs, as reported from research trials and in suckling commercial pigs where vaccine and field isolates are diverse. Additionally, killed combination vaccines containing H3 viruses typically “block” the antibody response to the H1 antigen unless significant efforts are made to overcome this issue. Commercial vaccines have been constructed to adjust this either by multifold increases in H1 antigen, selection of masterseed strains which avoids the consequence, or both. This is difficult to evaluate with multivalent autogenous vaccines without field trials to measure antibody responses in each new batch. In the Midwest, where most isolates are H1s, adding an H3 to the vaccine could cause vaccination failure. Without evaluating the antibody responses, the value of these interventions is unknown.

Also needed are vaccines that avoid the blocking effect of maternal antibodies, a major cause of failure of killed vaccines. The blocking issue can easily be overcome by applying vaccines at older nursery or grower ages. However, without extensive and transparent surveillance, there is no effective way to choose the antigen or antigens to be applied.

There is much we don’t know or understand about flu, but the recent pandemic journey promises hope of resolution. Vaccination strategies that work for other viruses are not applicable. There is need for significant field and bench research, an extensive national and regional surveillance program, and the dollars to support it. An opportunity for modified-live or vectored antigen delivery systems awaits us and the industry. It behooves the holders of the “One World – One Health” exchequer to provide this opportunity.

–Butch Baker, DVM