A highly efficacious live attenuated mumps virus–based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike

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.

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

“…Although systemic immunity of these vaccines is often thoroughly compared, e.g (116), their mucosal components are much less explored, e.g (93,117). Many more of different introduction routes are in clinical trails and development, including mucosal administration, holding a promise of eliciting long-term, broad, and potentially sterilizing immunity, e.g (71,72,(118)(119)(120)(121)(122)(123).…”

Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS‐CoV‐2 infection

“…In MuV expression system, preS‐6P had approximately sixfold higher protein expression than preS‐2P in MuV. rMuV‐preS‐6P induced 8.5‐fold higher NAb than rMuV‐preS‐2P in mice 8 . Similar to the MeV system, rMuV‐preS‐6P provided complete protection against MA SARS‐CoV‐2 challenge 8 .…”

“…SARS-CoV-2 S-specific serum IgG was determined by ELISA using SARS-CoV-2 preS-6P protein as the coating antigen described in our previous publications. 8,18,25 Two-fold serially diluted serum samples were used for ELISA. Endpoint titers were determined as the reciprocal of the highest dilution that had an absorbance value 2.1 folds greater than the background level (normal control serum).…”

A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters

“…Hence, a longer interval of 60 days between two doses followed by a challenge on day 90 was explored in our hamster study. A mumps vectored vaccine has been demonstrated to work well in animal models [ 30 ]. However, use of a vaccine strain with established safety and efficacy would be relatively quicker to deploy for routine immunization compared to new vectored vaccines.…”