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HSV-2 gC2 mRNA immunization in mice protects by producing antibodies that bind immune evasion epitopes

Hook LM, Cairns TM, Awasthi S, Egan KP, Gopalakrishnan M, Syeda Z, Pardi N, Bergstrom T, et al. · PLoS pathogens · 2026 Peer-reviewed Animal study DOI

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DOI: 10.1371/journal.ppat.1014337 · PMID: 42348550

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A mouse study of an HSV-2 gC2 nucleoside-modified mRNA-LNP vaccine component reports protection against intravaginal HSV-2 challenge, including at the lowest dose tested. Passive transfer of gC2 monoclonal antibodies protected when the antibodies blocked C3b binding, while a neutralizing antibody that did not block C3b binding failed to protect. The experiments described were done in mice.

Our summary is based on the published abstract only; the full data may add detail or caveats.

The authors describe their genital herpes vaccine candidate as including three immunogens, and this paper focuses on gC2. gC2 is described as an immune evasion molecule that inhibits complement activation by binding C3b. Antibody responses were measured against six gC2 epitopes, and both neutralizing and C3b-binding epitopes were targeted.

The authors conclude that a vaccine immunogen should induce antibodies that block the ability of gC to inhibit complement activation. These are animal findings, and protection in mice does not establish protection in people.

Sources

  1. HSV-2 gC2 mRNA immunization in mice protects by producing antibodies that bind immune evasion epitopes — PLoS pathogens , 2026
How this entry was checked

This entry was drafted with AI assistance and then checked. Every statement below was matched, word for word, to a passage in the abstract of the source by software (10 passages and 4 numbers traced). A separate AI pass, run independently and shown only the source and the statements, then tried to find errors (supported by the source, Sep 29, 2026). The editor (Mark) read and approved it on Sep 30, 2026. This is an editorial check, not peer review.

  1. Mice were immunized with five different doses of a gC2 nucleoside-modified mRNA-LNP vaccine and then challenged intravaginally with HSV-2. — source P1, P1; Supported by the source
  2. The authors report that the gC2 mRNA-LNP was highly protective as a single immunogen, even at the lowest dose. — source P1; Supported by the source
  3. Antibody responses were measured against six gC2 epitopes; both neutralizing and C3b-binding epitopes were targeted. — source P1, P1; Supported by the source
  4. In passive transfer of gC2 monoclonal antibodies, those that blocked C3b binding were protective, while a neutralizing antibody that did not block C3b binding failed to protect. — source P1, P1; Supported by the source
  5. gC2 is described as an immune evasion molecule that inhibits complement activation by binding C3b. — source P1; Supported by the source
  6. The authors describe their genital herpes vaccine candidate as including three immunogens involved in virus entry and immune evasion; this paper focuses on gC2. — source P1; Supported by the source
  7. The authors conclude that a vaccine immunogen should induce antibodies that block gC's inhibition of complement activation. — source P1; Supported by the source

Limits noted: abstract only, animal model.

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