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

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.ImportanceWith 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.

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases

“…When CVXGA1 was administered as a booster following two doses of a COVID-19 mRNA vaccine, PIV5-vectored vaccines generate higher levels of cross-reactive NAbs compared to three doses of COVID-19 mRNA vaccine. 164 These results indicate that CVXGA1 could serve as a booster vaccine against emerging variants. CVXGA1 is currently under Phase I clinical trial in the United States (NCT04954287).…”

“…The animal challenge study confirmed this phenomenon. 164 When hamsters were challenged at 9 months post vaccination, CVXGA1 immunized hamsters were well protected than mRNA vaccine. The live-attenuated MeV vaccine has also been proven to elicit long-lasting B-cell and T-cell responses, with a reported measles-specific antibody half-life of more than 200 years.…”

The End or a New Era of Development of SARS-CoV-2 Virus: Genetic Variants Responsible for Severe COVID-19 and Clinical Efficacy of the Most Commonly Used Vaccines in Clinical Practice

“…Even last fall, two nasal COVID-19 vaccination formulations were approved for use in India and China, although their approval has not yet been applied for in Europe. These contain modified adenoviruses that are self-attenuating and, according to the results of the Phase 1 clinical trial, they provide strong protection against SARS-CoV-2 infection [ 9 , 10 ]. In addition, mucosal vaccines against COVID-19 continue to be discussed and developed as potential players in controlling the pandemic [ 11 , 12 , 13 ].…”

“…Natural selection plays a vital role in the occurrence of new mutations. Mutations that amplify the reproduction, transmission, and immunity escape response could continue to increase if they help the viruses survive [ 10 ].…”