{"doi":"10.1101/2022.06.07.495215","title":"Efficacy of Parainfluenza Virus 5 (PIV5)-vectored Intranasal COVID-19 Vaccine as a Single Dose Vaccine and as a Booster against SARS-CoV-2 Variants","abstract":"Abstract Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has greatly reduced coronavirus disease 2019 (COVID-19)-related deaths and hospitalizations, but waning immunity and the emergence of variants capable of immune escape indicate the need for novel SARS-CoV-2 vaccines. An intranasal parainfluenza virus 5 (PIV5)-vectored COVID-19 vaccine CVXGA1 has been proven efficacious in animal models and blocks contact transmission of SARS-CoV-2 in ferrets. CVXGA1 vaccine is currently in human clinical trials in the United States. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccines expressing additional antigen SARS-CoV-2 nucleoprotein (N) or SARS-CoV-2 variant spike (S) proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well-maintained over time. When administered as a boost following two doses of a mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive neutralizing antibodies compared to three doses of a mRNA vaccine. In addition to the S protein, the N protein provides added protection as assessed by the highest body weight gain post-challenge infection. Our data indicates that PIV5-vectored COVID-19 vaccines, such as CVXGA1, can serve as booster vaccines against emerging variants. Importance With emerging new variants of concern (VOC), SARS-CoV 2 continues to be a major threat to human health. Approved COVID-19 vaccines have been less effective against these emerging VOCs. This work demonstrates the protective efficacy, and strong boosting effect, of a new intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297701,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":985828,"name":"Li Zhuo","orcid":"0000-0002-8780-7944","position":1,"is_corresponding":false},{"id":985829,"name":"Kelsey Briggs","orcid":"0000-0001-8368-5487","position":2,"is_corresponding":false},{"id":986240,"name":"María Cristina Huertas-Díaz","orcid":null,"position":3,"is_corresponding":false},{"id":986241,"name":"Elizabeth R. Wrobel","orcid":null,"position":4,"is_corresponding":false},{"id":986242,"name":"Maria Najera","orcid":null,"position":5,"is_corresponding":false},{"id":985830,"name":"Dong An","orcid":"0000-0002-7770-2284","position":6,"is_corresponding":false},{"id":875246,"name":"Nichole Orr‐Burks","orcid":"0000-0003-4713-2484","position":7,"is_corresponding":false},{"id":621421,"name":"Jackelyn Murray","orcid":"0000-0001-6838-3579","position":8,"is_corresponding":false},{"id":986243,"name":"Preetish Patil","orcid":null,"position":9,"is_corresponding":false},{"id":355921,"name":"Jiachen Huang","orcid":"0000-0001-7624-7390","position":10,"is_corresponding":false},{"id":296075,"name":"Jarrod J. Mousa","orcid":"0000-0003-4709-2478","position":11,"is_corresponding":false},{"id":866208,"name":"Linhui Hao","orcid":"0000-0002-7325-1009","position":12,"is_corresponding":false},{"id":245056,"name":"Tien-Ying Hsiang","orcid":"0000-0002-4316-4561","position":13,"is_corresponding":false},{"id":108916,"name":"Michael Gale","orcid":"0000-0002-6332-7436","position":14,"is_corresponding":false},{"id":986244,"name":"Stephen B. Harvey","orcid":null,"position":15,"is_corresponding":false},{"id":456496,"name":"S. Mark Tompkins","orcid":"0000-0002-1523-5588","position":16,"is_corresponding":false},{"id":986245,"name":"Robert Jeffrey Hogan","orcid":null,"position":17,"is_corresponding":false},{"id":581926,"name":"Eric R. Lafontaine","orcid":null,"position":18,"is_corresponding":false},{"id":174449,"name":"Hong Jin","orcid":null,"position":19,"is_corresponding":false},{"id":731232,"name":"Biao He","orcid":"0000-0001-8336-7171","position":20,"is_corresponding":false},{"id":731229,"name":"Ashley C. Beavis","orcid":"0000-0002-6345-4830","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":"35702147","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":[]}