{"doi":"10.3390/v17081136","title":"V4020 Venezuelan Equine Encephalitis Vaccine: Mitigating Neuroinvasion and Reversion Through Rational Design","abstract":"There is a need for safe and effective vaccines against the Venezuelan equine encephalitis virus that infects both humans and equines. However, development of a live-attenuated vaccine using the TC-83 strain has been hampered by substantial reactogenicity and the potential for neuroinvasion. In this study, we demonstrate that V4020, a new TC-83-based investigational VEEV vaccine with redundant safety features preventing neuroinvasion and reversion, exhibited no neuroinvasion potential in a murine model. Following subcutaneous or intramuscular administration, a subset of mice that received the TC-83 vaccine succumbed to central nervous system infection, with replicating virus detected in the CNS, demonstrating a low, yet detectable neuroinvasion potential of the TC-83 vaccine in vivo. Sequencing analysis of the TC-83 virus recovered from the brains identified a pseudoreversion of E2 R120I, as E2 R120 is known to confer attenuation for TC-83. In contrast, V4020 showed no evidence of virus in the CNS, highlighting one of the V4020 features, a new synonymous codon to minimize reversion to the wild-type residue. Overall, our study establishes V4020 as a rationally designed, safe vaccine candidate for VEEV with significantly reduced neuroinvasion risk.","journal":"Viruses","year":2025,"id":528686,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1407446,"name":"Koji Barnaby","orcid":null,"position":1,"is_corresponding":false},{"id":1264324,"name":"Sidney Goedeker","orcid":null,"position":2,"is_corresponding":false},{"id":1264325,"name":"A. R. Pignataro","orcid":null,"position":3,"is_corresponding":false},{"id":464771,"name":"Irina Tretyakova","orcid":null,"position":4,"is_corresponding":false},{"id":477561,"name":"Igor S. Lukashevich","orcid":"0000-0001-6523-5116","position":5,"is_corresponding":false},{"id":463945,"name":"Peter Pushko","orcid":"0000-0002-1073-6981","position":6,"is_corresponding":false},{"id":294630,"name":"Donghoon Chung","orcid":"0000-0003-2626-172X","position":7,"is_corresponding":false},{"id":1407445,"name":"Adrian Centers","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:50:52.565868Z","pmid":"40872849","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":[]}