Kening WangGeorgia D. TomarasSinthujan JegaskandaM. Anthony MoodyHua Xin LiaoKyle N. GoodmanPhillip W. BermanSupachai Rerks-NgarmPunnee PitisuttithumSorachai NitayapanJaranit KaewkungwalBarton F. HaynesJeffrey I. CohenaNational Institute of Allergy and Infectious DiseasesDuke University School of MedicineUniversity of California, Santa CruzThailand Ministry of Public HealthMahidol UniversityRoyal Thai ArmyUniversity of Melbourne2018-12-212019-03-142018-12-212019-03-142017-10-01Journal of Virology. Vol.91, No.19 (2017)109855140022538X2-s2.0-85029208639https://repository.li.mahidol.ac.th/handle/20.500.14594/41345© 2017 American Society for Microbiology. The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection, as well as antibodies to HSV. We derived monoclonal antibodies (MAbs) from peripheral blood B cells of recipients of the RV144 HIV vaccine and showed that these antibodies neutralized HSV-1 infection in cells expressing HVEM, but not the other major virus receptor, nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and mice that received the MAbs and were then challenged by corneal inoculation with HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, this is the first description of MAbs derived from human recipients of a vaccine that specifically target the HVEM binding site of gD. In summary, we found that monoclonal antibodies derived from humans vaccinated with the HVEM binding domain of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner, (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected mice.Mahidol UniversityAgricultural and Biological SciencesImmunology and MicrobiologyArticleSCOPUS10.1128/JVI.00411-17