Phylogenetic and antigenic analysis of influenza A(H3N2) viruses isolated from conscripts receiving influenza vaccine prior to the epidemic season of 1998/9

Abstract

Roughly half (54%) of the 910 young conscripts at a garrison in Finland were vaccinated with commercial influenza vaccines in autumn 1998. During the influenza outbreak in February 1999, 12 H3N2-subtype virus strains were isolated from vaccinated patients, and 11 such strains were isolated from unvaccinated patients. The isolates were related to the vaccine strain A/Sydney/5/97 and could be classified into three subgroups based on sequence variation in the HA1 gene coding for the variable domain of viral haemagglutinin (HA). A total of 6–10 amino-acid substitutions in HA1, three of these in the receptor-binding site, differentiated the field strains from the vaccine virus. In haemagglutination inhibition (HI) tests, eight strains from the study population exhibited reduced reactivity with a variety of antisera including human post-vaccination sera. Six of these strains were isolated from vaccinated and two from unvaccinated patients. The reduced reactivity did not correlate with particular amino-acid changes in HA1. We suggest that low-reactivity viruses may have an advantage over other co-circulating variants under some circumstances characterized by enhanced immunity-mediated selection and high infection pressure. Whether the frequency of these viruses increased in our vaccinated study population cannot be determined, nor can their effect on vaccine efficacy.