tetano
Editor, Senior Moderator
J Infect Dis
. 2024 May 9:jiae258.
doi: 10.1093/infdis/jiae258. Online ahead of print. Humoral correlates of protection against influenza A H3N2 virus infection
Gregory Hoy[SUP] 1 [/SUP], Daniel Stadlbauer[SUP] 2 [/SUP], Angel Balmaseda[SUP] 3 4 [/SUP], Guillermina Kuan[SUP] 3 5 [/SUP], Roger López[SUP] 3 4 [/SUP], Juan Manuel Carreno Quiroz[SUP] 2 [/SUP], Sergio Ojeda[SUP] 3 [/SUP], Nery Sánchez[SUP] 3 [/SUP], Temima Yellin[SUP] 2 [/SUP], Miguel Plazaola[SUP] 3 [/SUP], Aaron Frutos[SUP] 1 [/SUP], Florian Krammer[SUP] 2 6 7 8 [/SUP], Aubree Gordon[SUP] 1 [/SUP]
Affiliations
Background: 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 sub-dominant region, has not been established for influenza virus A/H3N2.
Methods: Household transmission studies were conducted in Managua, Nicaragua across three influenza seasons. Household contacts were tested for influenza virus infection using RT-PCR. We compared pre-existing antibody levels against full-length hemagglutinin (FLHA), HA stalk, and neuraminidase (NA) measured by enzyme-linked immunosorbent assay (ELISA), along with HA inhibition assay (HAI) titers, between infected and uninfected participants.
Results: A total of 899 individuals participated in household activation, with 329 infections occurring. A four-fold increase in initial HA stalk titers was independently associated with an 18% decrease in the risk of infection (OR=0.82, 95%CI 0.68-0.98, p=0.04). In adults, anti-HA stalk antibodies were independently associated with protection (OR=0.72, 95%CI 0.54-0.95, p=0.02). However, in 0-14-year-olds, anti-NA antibodies (OR=0.67, 95%CI 0.53-0.85, p<0.01) were associated with protection against infection, but anti-HA stalk antibodies were not.
Conclusions: 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.
Keywords: correlates of protection; global health; influenza; vaccination.
. 2024 May 9:jiae258.
doi: 10.1093/infdis/jiae258. Online ahead of print. Humoral correlates of protection against influenza A H3N2 virus infection
Gregory Hoy[SUP] 1 [/SUP], Daniel Stadlbauer[SUP] 2 [/SUP], Angel Balmaseda[SUP] 3 4 [/SUP], Guillermina Kuan[SUP] 3 5 [/SUP], Roger López[SUP] 3 4 [/SUP], Juan Manuel Carreno Quiroz[SUP] 2 [/SUP], Sergio Ojeda[SUP] 3 [/SUP], Nery Sánchez[SUP] 3 [/SUP], Temima Yellin[SUP] 2 [/SUP], Miguel Plazaola[SUP] 3 [/SUP], Aaron Frutos[SUP] 1 [/SUP], Florian Krammer[SUP] 2 6 7 8 [/SUP], Aubree Gordon[SUP] 1 [/SUP]
Affiliations
- PMID: 38723107
- DOI: 10.1093/infdis/jiae258
Background: 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 sub-dominant region, has not been established for influenza virus A/H3N2.
Methods: Household transmission studies were conducted in Managua, Nicaragua across three influenza seasons. Household contacts were tested for influenza virus infection using RT-PCR. We compared pre-existing antibody levels against full-length hemagglutinin (FLHA), HA stalk, and neuraminidase (NA) measured by enzyme-linked immunosorbent assay (ELISA), along with HA inhibition assay (HAI) titers, between infected and uninfected participants.
Results: A total of 899 individuals participated in household activation, with 329 infections occurring. A four-fold increase in initial HA stalk titers was independently associated with an 18% decrease in the risk of infection (OR=0.82, 95%CI 0.68-0.98, p=0.04). In adults, anti-HA stalk antibodies were independently associated with protection (OR=0.72, 95%CI 0.54-0.95, p=0.02). However, in 0-14-year-olds, anti-NA antibodies (OR=0.67, 95%CI 0.53-0.85, p<0.01) were associated with protection against infection, but anti-HA stalk antibodies were not.
Conclusions: 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.
Keywords: correlates of protection; global health; influenza; vaccination.