TY - JOUR T1 - 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. AU - Beavis,Ashley C, AU - Li,Zhuo, AU - Briggs,Kelsey, AU - Huertas-Díaz,María Cristina, AU - Wrobel,Elizabeth R, AU - Najera,Maria, AU - An,Dong, AU - Orr-Burks,Nichole, AU - Murray,Jackelyn, AU - Patil,Preetish, AU - Huang,Jiachen, AU - Mousa,Jarrod, AU - Hao,Linhui, AU - Hsiang,Tien-Ying, AU - Gale,Michael, AU - Harvey,Stephen B, AU - Tompkins,S Mark, AU - Hogan,Robert Jeffrey, AU - Lafontaine,Eric R, AU - Jin,Hong, AU - He,Biao, Y1 - 2022/06/08/ PY - 2022/6/15/entrez PY - 2022/6/16/pubmed PY - 2022/6/16/medline JF - bioRxiv : the preprint server for biology JO - bioRxiv N2 - : 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. UR - https://www.unboundmedicine.com/medline/citation/35702147/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_ DB - PRIME DP - Unbound Medicine ER -