{"doi":"10.3390/v14030540","title":"Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine","abstract":"The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 μg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 μg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 μg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 μg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-μg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 μg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.","journal":"Viruses","year":2022,"id":257332,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.965,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":412217,"name":"Sita Awasthi","orcid":"0000-0001-8230-3635","position":1,"is_corresponding":false},{"id":394962,"name":"Tina M. Cairns","orcid":"0000-0002-6112-6964","position":2,"is_corresponding":false},{"id":231967,"name":"Mohamad‐Gabriel Alameh","orcid":"0000-0002-5672-6930","position":3,"is_corresponding":false},{"id":907770,"name":"Bernard T. Fowler","orcid":null,"position":4,"is_corresponding":false},{"id":412214,"name":"Kevin P. Egan","orcid":"0000-0002-6653-6110","position":5,"is_corresponding":false},{"id":852423,"name":"Molly M. H. Sung","orcid":"0000-0002-0874-0922","position":6,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":7,"is_corresponding":false},{"id":394965,"name":"Gary H. Cohen","orcid":"0000-0002-8581-8068","position":8,"is_corresponding":false},{"id":412216,"name":"Harvey M. Friedman","orcid":"0000-0002-0765-9460","position":9,"is_corresponding":false},{"id":412215,"name":"Lauren M. Hook","orcid":"0000-0002-5540-2459","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T00:25:30.183987Z","pmid":"35336946","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}