Age-related prevalence of serum hemagglutination-inhibition antibodies cross-reactive to 2012 and 2013 newly emerging swine-origin influenza A(H3N2) variant viruses (VIR5P.1134)

Abstract

Abstract Recent outbreaks of swine-origin influenza A(H3N2) variant virus (H3N2v) in the U.S., mainly among young children with swine exposure, have raised concerns. Previous studies demonstrated older children and young adults had the highest hemagglutination-inhibition (HI) antibodies (Ab) to 2011 H3N2v viruses. In 2013, newly emerging antigenic variants of H3N2v viruses, responsible for 18 human infections, acquired N145K/R mutations in hemagglutinin (HA). Here, human and postinfection ferret sera were tested in HI assays against 2012-13 H3N2v viruses possessing 145N, K or R HA mutations, together with nine historical seasonal H3N2 (sH3N2) viruses circulating since 1968. We found the H3N2v viruses were antigenically distinct but retained a low degree of serologic cross-reactivity (CR) (with ferret antisera) to sH3N2 viruses that circulated in 1990s. Across all age groups (6-80+ years), approximately half were seropositive (HI titer≥40) to the H3N2v viruses. The age related seroprevalence among children were likely associated with primary exposure to sH3N2 viruses in 1990s. We observed a single substitution at 145 in HA was sufficient to change an individual’s seropositivity to the virus and significantly influenced the seroprevalence in certain age groups. The susceptibility to 2012-13 H3N2v viruses remains high in young children, and low in older children and young adults. Improved knowledge of age-related CR Ab is critical for influenza risk assessment and pandemic preparedness.