ArticlePLoS pathogens2018
Vaccine-induced antibodies to herpes simplex virus glycoprotein D epitopes involved in virus entry and cell-to-cell spread correlate with protection against genital disease in guinea pigs.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 35 citations in OpenAlex.
- Glycoprotein G enables HSV-2 neuroinvasion and provides protection as a glycosylated vaccine antigen.PLoS pathogens · 2026Article
- Human herpesvirus evasion of humoral immunity and implications for vaccine development.Nature reviews. Microbiology · 2026Review
- HSV-2 gC2 mRNA immunization in mice protects by producing antibodies that bind immune evasion epitopes.PLoS pathogens · 2026Article
- Immunization with Herpes Simplex Virus Nanoparticles Targeting Both Attachment and Fusion Protect Against Infection.bioRxiv : the preprint server for biology · 2026Article
- Antibodies targeting HSV glycoprotein B require effector functions to protect neonatal mice.Journal of virology · 2026Article
- Host Immune Response Mechanisms Against Herpes Simplex Virus Type 2 Infection.Pathogens (Basel, Switzerland) · 2026Review
- Bispecific antibodies targeting herpes simplex virus glycoproteins B and D.Frontiers in immunology · 2026Article
- Distal and local mucosal immunization with a BoHV-4-based vector delivering CpHV-1 gD confers protection against intravaginal CpHV-1 challenge in goats.Frontiers in immunology · 2026Article
- Role of mucosal chemokines in the development of tissue-resident CD4Frontiers in immunology · 2026Review
- The Path Towards Effective Long-Lasting Tissue-Targeted Prime/Pull/Keep Herpes Simplex Therapeutic Vaccines.Vaccines · 2025Review
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- Article
- Boosting of vaginal HSV-2-specific B and T cell responses by intravaginal therapeutic immunization results in diminished recurrent HSV-2 disease.Journal of virology · 2023Article
- Article
- Cell-to-cell spread inhibiting antibodies constitute a correlate of protection against herpes simplex virus type 1 reactivations: A retrospective study.Frontiers in immunology · 2023Article
- Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice.Nature communications · 2022Article
- Maternally transferred mAbs protect neonatal mice from HSV-induced mortality and morbidity.The Journal of experimental medicine · 2022Article
- Moving beyond Titers.Vaccines · 2022Review
- Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine.Viruses · 2022Article
- Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models.The Journal of clinical investigation · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit antigen is included in many preclinical candidate vaccines. The rationale for including gD2 is to produce antibodies that block crucial gD2 epitopes involved in virus entry and cell-to-cell spread. HSV-2 gD2 was the only antigen in the Herpevac Trial for Women that protected against HSV-1 genital infection but not HSV-2. In that trial, a correlation was detected between gD2 ELISA titers and protection against HSV-1, supporting the importance of antibodies. A possible explanation for the lack of protection against HSV-2 was that HSV-2 neutralization titers were low, four-fold lower than to HSV-1. Here, we evaluated neutralization titers and epitope-specific antibody responses to crucial gD2 epitopes involved in virus entry and cell-to-cell spread as correlates of immune protection against genital lesions in immunized guinea pigs. We detected a strong correlation between neutralizing antibodies and protection against genital disease. We used a high throughput biosensor competition assay to measure epitope-specific responses to seven crucial gD2 linear and conformational epitopes involved in virus entry and spread. Some animals produced antibodies to most crucial epitopes while others produced antibodies to few. The number of epitopes recognized by guinea pig immune serum correlated with protection against genital lesions. We confirmed the importance of antibodies to each crucial epitope using monoclonal antibody passive transfer that improved survival and reduced genital disease in mice after HSV-2 genital challenge. We re-evaluated our prior study of epitope-specific antibody responses in women in the Herpevac Trial. Humans produced antibodies that blocked significantly fewer crucial gD2 epitopes than guinea pigs, and antibody responses in humans to some linear epitopes were virtually absent. Neutralizing antibody titers and epitope-specific antibody responses are important immune parameters to evaluate in future Phase I/II prophylactic human vaccine trials that contain gD2 antigen.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.