The limited effectiveness of the 2016-2017 influenza vaccine may be due to a glycoprotein mutation in fertilized chicken eggs, a study in PNAS reports.
Accompanying vaccines to the current H3N2 influenza viruses lack the new antigenic glycosylation site B in hemagglutinin (HA) glycoproteins, rendering them weak in treating patients, according to Seth J Zost, MS, of the Department of Microbiology at the Perelman School of Medicine at the University of Pennsylvania and associates.
The researchers sought to determine the cause of the mismatch between vaccine and virus in the 2016-2017 influenza season. The investigators hypothesized that the difference in the new glycosylation site inhibits the binding of antibodies to the antigenic site B of HA, which only recognize epitopes unassociated with site B.
In most mismatched vaccines from 1968 to 2013, the majority of neutralizing antibodies associated with H3N2 targeted the H3 globular head. It was not until the 2014-2015 flu season that researchers believed H3N2 viruses developed new glycosylation sites other than the antigenic H3 region (3C.2a clade). A missense mutation, K160T, changed almost all H3N2 circulating viruses, suggesting an N-linked glycosylation site in the antigenic site B of HA.
In the 2016-2017 season, the H3N2 flu vaccine was updated to include the new antigens, but it was only 43% effective; its effectiveness was particularly low in younger ages when testing in adults aged 18 to 49. This might be a consequence of repeated vaccines that can result in lower antibody response, reducing the effectiveness of the vaccine.
The authors compared the current H3N2 vaccine strain with the circulating H3N2 virus strain to study the ineffectiveness in the current vaccine through reverse mutation of the H3N2 strain to generate viruses with either threonine or lysine at the 160 residue.
Fertile chicken egg-adapted vaccines did not have the site B glycosylation sites possessed by spreading 3C.2a H3N2 strains. These mutations mainly occur in the HA, which cause viral adherence to the chicken cells. The researchers found a HA mutation in the egg-grown H3N2 vaccine strain, which changes antigenicity causing very poor virus counteraction in humans hosts.
The generated vaccine antigens K160 and T160 stimulated different responses in humans. A baculovirus-prepared vaccine, containing T160 HA, elicited a significantly higher fold change in antibody response in some patients than the vaccine antigens containing K160, the authors reported. Younger adults were able to generate antibodies effectively for K160 HA epitopes but not for T160 HA after vaccination.
Due to the uneven distribution of successful and failed baculovirus-prepared vaccinations, the researchers concluded that the higher antibody response was in the detection of viruses with the T160 HA site but not necessarily other epitopes.
“A major effort should be made to develop and utilize new systems that produce influenza antigens that are not dependent on egg or cell culture-adaptive mutations,” the researchers stated. “Antigens that do not possess adaptive mutations will likely offer better protection against influenza virus strains that circulate in the human population.”
Zost SJ, Parkhouse K, Gumina ME, et al. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains [published online November 6, 2017]. Proc Natl Acad Sci USA. doi:10.1073/pnas.1712377114
This article originally appeared on Clinical Advisor