Universal Influenza Vaccine Would Mitigate Seasonal & Pandemic Flu

Although currently available vaccines for influenza have proved effective at reducing incidence of seasonal infection—at least among those who avail themselves of these options—researchers continue to seek even greater protection against seasonal and pandemic strains, through the development of so-called “universal” vaccines.

At present, existing vaccines are designed to bolster antibodies against the hemagglutinin (HA) and neuraminidase (NA) surface proteins of circulating strains. However, there are challenges inherent in this approach, not least among them the fact that the HA and NA characteristics of individual strains are effectively moving targets and that, as a result, influenza vaccines need to be modified regularly. Existing seasonal vaccines are also ineffective against pandemic influenza, as it is impossible to predict in advance the types of strains that will cause such mass outbreaks.

Conversely, universal vaccines are designed to target “more conserved components of the influenza virus,” the authors of a new paper published online by the journal PLOS Computational Biology write, thereby potentially providing protection against all influenza A strains and subtypes. The authors, from the University of Chicago, Princeton University, and Imperial College, London, developed a mathematical model designed to analyze and predict “transmission dynamics and antigenic evolution of influenza” to assess how these novel vaccines might compare to existing seasonal vaccines in terms of uptake, seasonal influenza incidence reduction, and, of course, pandemic influenza prevention.

“Many universal vaccine candidates are showing promising signs in the laboratory, but it will be some years before we can see universal vaccines being licensed for use in humans,” lead author Rahul Subramanian, a graduate student in the University of Chicago’s Department of Ecology and Evolution, told Contagion. “One aspect of our work is to try and cast light on some of the important things to monitor on this route to development.”

The model Subramanian and colleagues developed has two components: an “epidemic component,” designed to predict levels of immunity resulting from vaccination and natural infection, and an “interepidemic component,” designed to predict the effects of “antigenic drift; waning of cross-protective immunity, and population turnover” on immunity levels. While the model showed that both existing seasonal vaccines and universal vaccines in development effectively reduce seasonal epidemics, at any level of coverage, the authors found that universal vaccines appear to have a stronger effect, and that universal vaccination would “slow antigenic evolution over several seasons,” driving it to 0 at high coverage.

The model also revealed that while high coverage with seasonal vaccines allows “for increased pandemic sizes,” universal vaccines would have the opposite effect, with pandemic sizes declining more rapidly “with increasing universal vaccination coverage when there is no antigenic evolution.” The authors attribute this to the fact that “interrupting transmission renders vaccination the sole source of cross-protective immunity in the population.”

The authors write, “We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread.”

“A future vaccination program that uses universal vaccines could have very different effects compared to one that uses conventional vaccines,” Subramanian added. “For example, a universal vaccination program could control seasonal influenza epidemics to a greater extent than conventional programs with the same population coverage. Part of the reason is that universal vaccination tends to dampen influenza evolution, or the genetic changes by which the virus can escape immunity, while conventional vaccines could do the opposite.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.