Strain Selection for Annual Influenza Vaccines Should Consider Preexisting Immunity

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The "naive" ferret model currently used for vaccine strain selection does not recapitulate the complexity of human preexisting immunity.
The "naive" ferret model currently used for vaccine strain selection does not recapitulate the complexity of human preexisting immunity.

Repeated exposure to the influenza virus affects antibody quantity and quality, and strains selected for seasonal vaccines may not provide coverage sufficient for individuals frequently infected and/or vaccinated, according to findings published in Clinical Infectious Diseases.

Influenza-specific immunity in humans is complex, because it is affected by previous exposures to natural infections as well as annual vaccination. The study authors noted that reduced seasonal influenza vaccine effectiveness was observed in individuals who received repeated vaccines every year. In the study, the researchers examined influenza A/H3 specific cross-reactivity, using blood samples from individuals who had received a vaccine. In addition, the effect of prior influenza H3 virus exposures on antibody development was also investigated in a ferret model.

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Results demonstrated that serous fluid samples from individuals after vaccination, with or without preexisting immunity, demonstrated different cross-reactivity against influenza H3 virus variants. The extent of cross-reactive ferret antibodies induced by repeated exposure to influenza H3 also increased, and antigenic variations between influenza H3 viruses characterized by ferret antisera decreased as the number of exposures increased. Although repeated exposure to influenza H3 induced the so-called "original antigenic sin" phenomena in hemagglutination inhibition assay titers against exposure to viruses later on, the ferret antibodies showed gradually enhanced avidity for different H3/hemagglutinin. This rise in antibody avidity inversely correlated with reduced antigenic differences among H3 viruses characterized.

"Vaccine strains selected [by this ferret model] may not provide coverage sufficient for those with frequent vaccinations/infections, resulting in the compromised [vaccine effectiveness] observed," wrote the study authors.

Reference

Kosikova M, Li L, Radvak P, Ye Z, Wan XF, Xie H. Imprinting of repeated influenza A/H3 exposures on antibody quantity and antibody quality: implications  on seasonal vaccine strain selection and vaccine performance [published online August 31, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy327

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