Infectious disease experts from the US National Institutes of Health and the World Health Organization (WHO) warn that current methods to seasonal influenza vaccine development have kept America relatively defenceless against the influenza A (H3N2) strain now making its way over from the Southern hemisphere.
Writing in a recent perspectives article in the New England Journal of Medicine, the authors, including Catharine I. Paules, MD, and Anthony S. Fauci, MD, from the Office of the Director, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, and Sheena G. Sullivan, MPH, PhD, and Kanta Subbarao, MB, MPH, from the WHO Collaborating Center for Reference and Research on Influenza, Melbourne, Australia, say data from the recent influenza season in Australia should put america on alert regarding the upcoming influenza season.
Moreover, they require a “transformative approach” to a universal vaccine, instead of the seasonal, strain-specific one currently used. In addition they recommend ditching egg-based vaccine propagation in support of cell culture or the recombinant DNA baculovirus system.
Dr Paules and co-workers note that confirmed influenza cases in Australia reached 215,280 by mid-October, which is dramatically greater than the 59,000 cases reported through the 2009 pandemic.
And if that were not sufficiently unwelcome news, the authors further remember that preliminary data place the H3N2 vaccine efficacy at about 10%. This is the same vaccine currently being used in America.
One factor in this dismal efficacy is regarded as a mismatch between strain-specific vaccines recommended by the WHO and the circulating influenza strains. However, “even in years when influenza vaccines are well matched to circulating viruses, estimates of vaccine effectiveness range from 40 to 60%, which is lower than that for most licensed non-influenza vaccines,” Dr Paules and colleagues write.
Another factor for low efficacy is that a lot of influenza-vaccine viruses are propagated in eggs, and the vaccine virus changes during egg-based production in manners that facilitate replication in eggs but reduce vaccine effectiveness against circulating virus.
A key change seems to be a mutation in the hemagglutinin (HA) protein that mediates receptor binding by neutralizing antibodies, according to a recent study from researchers at the Perelman School of Medicine, University of Pennsylvania, Philadelphia. The researchers identified an HA glucosylation site that was shed during egg adaptation but remained in circulating influenza A (H3N2) strains.
That difference between the vaccine and circulating strains may have contributed to low vaccine efficacy through the 2016-2017 season in the USA. Corroborating that view, the team discovered that most participants who had a solid antibody response to the circulating strains had received a vaccine produced in a recombinant DNA baculovirus system, which does not trigger viral changes.
Preliminary data propose that egg adaptation changes in HA may also have contributed to the poor vaccine efficacy in the recent Australian influenza season, according to Dr Paules and colleagues.
Because most of the united states influenza-vaccine supply is produced in eggs and the 2017-2018 Northern Hemisphere vaccine is similar to that used in Australia, the outcome may be poor vaccine effectiveness against influenza A (H3N2) viruses and a comparatively severe influenza season in the USA.
“This possibility underscores the need to strive toward a ‘universal’ influenza vaccine that will protect against seasonal influenza drift variants as well as potential pandemic strains, with better durability than current annual vaccines,” the authors conclude. “Among other advantages, in all likelihood, such a vaccine would not be subject to the limitations of egg-based vaccine technology.”
“What encourages me about this piece is the acknowledgement that the 1930s influenza vaccine technology is not really up to the task,” Heath A. Kelly, MD, adjunct professor of infectious disease epidemiology at the National Centre for Epidemiology and Population Health, Australian National University in Canberra, informed Medscape Medical News.
“When I first started researching influenza vaccine effectiveness, it was evident that killed sub-unit vaccines did not seem to reflect the marketing hype. This was at a time when both the CDC [Centers for Disease Control and Prevention] and the WHO were claiming that influenza vaccines were 70% effective, a claim that was difficult to sustain…. It is understandable that public health authorities would not want to undermine confidence in vaccines in general and influenza vaccines in particular, but it is an open question whether overstating influenza vaccine effectiveness is good for public confidence. That is why it is refreshing to see an honest statement of the problem.”
Dr Kelly added, “There is absolutely no doubt we need a different approach to vaccine development and manufacture, but if the technology were easy, we would have it sorted by now.”