A highly efficacious live attenuated mumps virus–based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike
Yuexiu Zhang, Mijia Lu, Mahesh KC, Eunsoo Kim, Mohamed M. Shamseldin, Chengjin Ye, Piyush Dravid, Michelle Chamblee, Jun‐Gyu Park, Jesse M. Hall, Sheetal Trivedi, Supranee Chaiwatpongsakorn, Adam D. Kenny, Satyapramod Murthy, Himanshu Sharma, Xueya Liang, Jacob S. Yount, Amit Kapoor, Luis Martínez‐Sobrido, Purnima Dubey, Prosper N. Boyaka, Mark E. Peeples, Jiànróng Lǐ
Abstract
With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)–based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P–M or F–SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P–M gene junction was more efficient than from the F–SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1 −/− mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.