학술논문
Humoral correlates of protection against influenza A H3N2 virus infection.
Document Type
Academic Journal
Author
Hoy G; School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.; Stadlbauer D; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Balmaseda A; Sustainable Sciences Institute, Managua, Nicaragua.; Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua.; Kuan G; Sustainable Sciences Institute, Managua, Nicaragua.; Centro de Salud Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua.; López R; Sustainable Sciences Institute, Managua, Nicaragua.; Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua.; Carreno Quiroz JM; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ojeda S; Sustainable Sciences Institute, Managua, Nicaragua.; Sánchez N; Sustainable Sciences Institute, Managua, Nicaragua.; Yellin T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Plazaola M; Sustainable Sciences Institute, Managua, Nicaragua.; Frutos A; School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.; Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria.; Gordon A; School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)