https://orcid.org/0000-0001-9512-7941
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Gregory Hoy, Daniel Stadlbauer, Angel Balmaseda, Guillermina Kuan, Roger López, Juan Manuel Carreno Quiroz, Sergio Ojeda, Nery Sánchez, Temima Yellin, Miguel Plazaola, Aaron Frutos, Florian Krammer, Aubree Gordon, Humoral Correlates of Protection Against Influenza A/H3N2 Virus Infection, The Journal of Infectious Diseases, 2024;, jiae258, https://doi.org/10.1093/infdis/jiae258
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Abstract
Influenza virus remains a threat to human health, but gaps remain in our knowledge of the humoral correlates of protection against influenza virus A/H3N2, limiting our ability to generate effective, broadly protective vaccines. The role of antibodies against the hemagglutinin (HA) stalk, a highly conserved but immunologically subdominant region, has not been established for influenza virus A/H3N2.
Household transmission studies were conducted in Managua, Nicaragua, across 3 influenza seasons. Household contacts were tested for influenza virus infection using reverse-transcription polymerase chain reaction. We compared preexisting antibody levels against full-length HA, HA stalk, and neuraminidase (NA) measured by enzyme-linked immunosorbent assay, along with hemagglutination inhibition assay titers, between infected and uninfected participants.
A total of 899 individuals participated in household activation, with 329 infections occurring. A 4-fold increase in initial HA stalk titers was independently associated with an 18% decrease in the risk of infection (adjusted odds ratio [aOR], 0.82 [95% confidence interval {CI}, .68–.98]; P = .04). In adults, anti-HA stalk antibodies were independently associated with protection (aOR, 0.72 [95% CI, .54–.95]; P = .02). However, in 0- to 14-year-olds, anti-NA antibodies (aOR, 0.67 [95% CI, .53–.85]; P < .01) were associated with protection against infection, but anti-HA stalk antibodies were not.
The HA stalk is an independent correlate of protection against A/H3N2 infection, though this association is age dependent. Our results support the continued exploration of the HA stalk as a target for broadly protective influenza vaccines but suggest that the relative benefits may depend on age and influenza virus exposure history.
