{"doi":"10.1128/jvi.01989-24","title":"Efficacy of parainfluenza virus 5 (PIV5)-vectored intranasal COVID-19 vaccine as a single dose primer and booster against SARS-CoV-2 variants","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:sec>\n            <jats:title/>\n            <jats:p>Immunization with COVID-19 vaccines has greatly reduced COVID-19-related deaths and hospitalizations from SARS-CoV-2 infection, but waning immunity and the emergence of variants capable of immune escape indicate the need for annual vaccine updates or development of different SARS-CoV-2 vaccine platforms. Parainfluenza virus 5 (PIV5)-vectored intranasal COVID-19 vaccine with the ancestral spike (S) protein (CVXGA1) has been shown to be a promising next-generation COVID-19 vaccine preclinically and is currently being evaluated in humans. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccine candidates expressing additional SARS-CoV-2 nucleoprotein (N) antigen or SARS-CoV-2 variant 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 (nAbs) 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 booster following two doses of an mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive nAbs than three doses of mRNA vaccine. Our data indicate that an intranasal PIV5-vectored COVID-19 vaccine can serve as a booster vaccine against emerging variants.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE</jats:title>\n            <jats:p>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 an intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters. Our intranasal vaccine can act as an effective booster for individuals already 58 vaccinated against SARS-CoV-2.</jats:p>\n          </jats:sec>","journal":"Journal of Virology","year":2025,"id":634374,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":581553,"name":"Zhuo Li","orcid":"0000-0001-8774-0471","position":1,"is_corresponding":false},{"id":985829,"name":"Kelsey Briggs","orcid":"0000-0001-8368-5487","position":2,"is_corresponding":false},{"id":1176746,"name":"María Cristina Gingerich","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":1474796,"name":"Dong An","orcid":"0000-0002-8389-987X","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":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Efficacy of parainfluenza virus 5 (PIV5)-vectored intranasal COVID-19 vaccine as a single dose primer and booster against SARS-CoV-2 variants","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:sec>\n            <jats:title/>\n            <jats:p>Immunization with COVID-19 vaccines has greatly reduced COVID-19-related deaths and hospitalizations from SARS-CoV-2 infection, but waning immunity and the emergence of variants capable of immune escape indicate the need for annual vaccine updates or development of different SARS-CoV-2 vaccine platforms. Parainfluenza virus 5 (PIV5)-vectored intranasal COVID-19 vaccine with the ancestral spike (S) protein (CVXGA1) has been shown to be a promising next-generation COVID-19 vaccine preclinically and is currently being evaluated in humans. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccine candidates expressing additional SARS-CoV-2 nucleoprotein (N) antigen or SARS-CoV-2 variant 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 (nAbs) 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 booster following two doses of an mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive nAbs than three doses of mRNA vaccine. Our data indicate that an intranasal PIV5-vectored COVID-19 vaccine can serve as a booster vaccine against emerging variants.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE</jats:title>\n            <jats:p>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 an intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters. Our intranasal vaccine can act as an effective booster for individuals already 58 vaccinated against SARS-CoV-2.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40116505","pmcid":"PMC11998504","openalex_id":"https://openalex.org/W4408690696","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"U01 AI151698","title":null},{"funder_name":"National Institutes of Health","grant_id":"3U01AI151698-03S2","title":"University of Washington Arboviral Research Network (UWARN)"}],"total_grants":2,"fwci":6.3609,"citation_percentile":0.96982333,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1128/jvi.01989-24","host_type":"journal"},{"url":"https://doi.org/10.1128/jvi.01989-24","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/jvi.01989-24","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40116505","host_type":"repository"},{"url":"https://doaj.org/article/75444db1191e404e850556fc051f3aaf","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11998504","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11998504","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11998504?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1128/jvi.01989-24","host_type":""}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","vaccines and immunoinformatics approaches","Respiratory viral infections research","Animals","SARS-CoV-2","COVID-19 Vaccines","Administration, Intranasal","COVID-19","Spike Glycoprotein, Coronavirus","Antibodies, Viral","Antibodies, Neutralizing","Parainfluenza Virus 5","Immunization, Secondary","Cricetinae","Mesocricetus","Humans","Genetic Vectors","Female","SARS-CoV-2 variants"],"mesh_terms":["COVID-19","SARS-CoV-2","COVID-19 Vaccines","Administration, Intranasal","Animals","Antibodies, Viral","Female","Genetic Vectors","Cricetinae","Humans","Immunization, Secondary","Mesocricetus","Parainfluenza Virus 5","Antibodies, Neutralizing","Spike Glycoprotein, Coronavirus"],"keywords":["Virology","Immunogenicity","Biology","Heterologous","Neutralizing antibody","Nasal administration","Vaccine efficacy","Virus","Antibody","Immunity","Booster dose","Immunization","Immune system","Immunology","Vaccination","Titer","Gene","Genetics","Golden Syrian Hamster","Viral-vectored Vaccine","Sars-cov-2","Parainfluenza Virus 5 (Piv5)","COVID-19 Vaccines","Mesocricetus","Genetic Vectors","Immunization, Secondary","COVID-19","Antibodies, Viral","Antibodies, Neutralizing","Cricetinae","Vaccines and Antiviral Agents","Spike Glycoprotein, Coronavirus","Parainfluenza Virus 5","Animals","Humans","Female","Administration, Intranasal"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:34:38.815639Z","pmid":null,"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":[]}