Immunogenicity of poxvirus A16/G9 entry–fusion subcomplex and its restriction by A56/K2 protein informs vaccine design
5 affiliations
- 1Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA. [email protected]
- 2Center for Information Technology, NIH, Bethesda, MD, USA
- 3Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA
- 4Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
- 5Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA. [email protected]
Abstract
Poxviruses rely on a conserved multiprotein entry-fusion complex, providing numerous potential antibody targets, although the immunogenicities of only a few have been analysed. Here we tested the ectodomains of ten orthopoxvirus entry-fusion complex proteins in rabbit and mouse immunization experiments and determined that six induce neutralizing antibodies. Focusing on the apical A16/G9 heterodimer, we show that it induces antibodies that prevent vaccinia virus (VACV) entry, cross-neutralize cowpox virus (CPXV) and monkeypox virus (MPXV), and protect mice against lethal challenge infections with VACV and CPXV. However, antibodies to A16/G9 had limited detection following infections with attenuated or virulent VACV, CPXV or MPXV, but were robustly induced upon immunization with recombinant VACVs secreting G9 or that have deletions of the genes encoding the viral fusion suppressor A56/K2 complex, which specifically binds A16/G9. Our work identifies previously unrecognized immunogens for incorporation into recombinant vaccines and characterizes a mode of immune evasion via the A56/K2 complex.
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BibTeX
@article{yu2026immunogenicity,
title = {{Immunogenicity of poxvirus A16/G9 entry–fusion subcomplex and its restriction by A56/K2 protein informs vaccine design}},
author = {Huibin Yu and Wolfgang Resch and Catherine A. Cotter and Wei Xiao and Tase Karamanolis and Ahmed A. Belghith and Maxinne A. Ignacio and Patricia L. Earl and Gary H. Cohen and Bernard Moss},
journal = {Nature Microbiology},
year = {2026},
month = jun,
doi = {10.1038/s41564-026-02392-6},
url = {https://doi.org/10.1038/s41564-026-02392-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immunogenicity of poxvirus A16/G9 entry–fusion subcomplex and its restriction by A56/K2 protein informs vaccine design
AU - Huibin Yu
AU - Wolfgang Resch
AU - Catherine A. Cotter
AU - Wei Xiao
AU - Tase Karamanolis
AU - Ahmed A. Belghith
AU - Maxinne A. Ignacio
AU - Patricia L. Earl
AU - Gary H. Cohen
AU - Bernard Moss
PY - 2026
DA - 2026/06/10
JO - Nature Microbiology
DO - 10.1038/s41564-026-02392-6
UR - https://doi.org/10.1038/s41564-026-02392-6
AB - Poxviruses rely on a conserved multiprotein entry-fusion complex, providing numerous potential antibody targets, although the immunogenicities of only a few have been analysed. Here we tested the ectodomains of ten orthopoxvirus entry-fusion complex proteins in rabbit and mouse immunization experiments and determined that six induce neutralizing antibodies. Focusing on the apical A16/G9 heterodimer, we show that it induces antibodies that prevent vaccinia virus (VACV) entry, cross-neutralize cowpox virus (CPXV) and monkeypox virus (MPXV), and protect mice against lethal challenge infections with VACV and CPXV. However, antibodies to A16/G9 had limited detection following infections with attenuated or virulent VACV, CPXV or MPXV, but were robustly induced upon immunization with recombinant VACVs secreting G9 or that have deletions of the genes encoding the viral fusion suppressor A56/K2 complex, which specifically binds A16/G9. Our work identifies previously unrecognized immunogens for incorporation into recombinant vaccines and characterizes a mode of immune evasion via the A56/K2 complex.
SN - 2058-5276
ER -