A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease

• DOI: 10.1128/jvi.01762-23
• Publication Date: 2024-04-02T15:00:23Z
• Authors: Sham Nambulli; Nicolas Escriou; Linda J. Rennick; Matthew J. Demers; Natasha L. Tilsto...; Anita K. McElroy; Dominique J. Barbeau; Nicholas A. Cross...; Ryan M. Hoehl; Sabrina Schrauf; Alexander G. White; H. Jacob Borish; Jaime A. Tomko; Lonnie J. Frye; Charles A. Scanga; JoAnne L. Flynn; Annette Martin; Christiane Gerke; Amy L. Hartman; W. Paul Duprex
• Keywords: 2019-20 coronavirus outbreak; African Green Monkey; Coronavirus; Betacoronavirus

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for largest human pandemic in 100 years. Thirty-four vaccines are currently approved use worldwide, approximately 67% world population has received a complete primary series one, yet countries dealing with new waves infections, variant viruses continue to emerge, breakthrough infections frequent secondary waning immunity. Here, we evaluate measles virus (MV)-vectored vaccine expressing stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) demonstrated immunogenicity mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23 ]) an established African green monkey model disease. Animals were vaccinated V591 or control (an equivalent MV-vectored irrelevant antigen) intramuscularly using prime/boost schedule, followed by challenge early isolate 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well T cells. Following challenge, lower infectious viral (v) RNA loads mucosal secretions stopped shedding these earlier. vRNA gastrointestinal tract tissues necropsy. This correlated disease burden lungs quantified PET/CT late time points post-challenge pathological analysis IMPORTANCE Even though available, frequent, hesitancy persists. study uses safe effective platform vaccination against SARS-CoV-2. The candidate was used vaccinate monkeys (AGMs). All AGMs robust antigen-specific immune responses. After produced less secretions, shorter period, reduced compared animals. At necropsy, levels detected tissue samples from animals, lacked histologic hallmarks observed exclusively AGMs.