ABSTRACT Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed in record time and show excellent efficacy and effectiveness against coronavirus disease 2019 (COVID-19). However, currently approved vaccines cannot meet the global demand. In addition, none of the currently used vaccines is administered intranasally to potentially induce mucosal immunity. Here, we tested the safety and immunogenicity of a second-generation SARS-CoV-2 vaccine that includes a stabilized spike antigen and can be administered intranasally. The vaccine is based on a live Newcastle disease virus vector expressing a SARS-CoV-2 spike protein stabilized in a prefusion conformation with six beneficial proline substitutions (AVX/COVID-12-HEXAPRO; Patria). Immunogenicity testing in the pig model showed that both intranasal and intramuscular application of the vaccine as well as a combination of the two induced strong serum neutralizing antibody responses. Furthermore, substantial reactivity to B.1.1.7, B.1.351, and P.1 spike variants was detected. Finally, no adverse reactions were found in the experimental animals at any dose level or delivery route. These results indicate that the experimental vaccine AVX/COVID-12-HEXAPRO (Patria) is safe and highly immunogenic in the pig model.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, spike, coronavirus vaccine, newcastle disease virus, NDV, PIGS, HexaPro, prolines, pig model, 【초록키워드】 coronavirus disease, Efficacy, coronavirus, immunogenicity, Immunity, B.1.351, SARS-CoV-2 vaccine, Antigen, B.1.1.7, P.1, SARS-CoV-2 spike protein, Effectiveness, intranasal, intramuscular, mucosal, Combination, dose, Adverse reaction, Safe, acute respiratory syndrome, immunogenic, Serum neutralizing antibody, prefusion conformation, Administered, responses, tested, include, intranasally, addition, approved, induce, reactivity, expressing, the vaccine, proline substitution, spike variant, 【제목키워드】 immunogenicity, Safety, pig, candidate,