RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.
RESUMO
Respiratory syncytial virus (RSV) infection causes considerable mortality and morbidity in infants and young children. RSV infection appears to elicit a mixed immune response characterized by both Th1-type cells and Th2-type cells. This immune response, along with clinical features such as bronchiolitis, wheezing, and respiratory distress caused by RSV infection, presents similarly to many features of asthma and has led to an investigation into the link between severe RSV infection and asthma. RSV infection in mice is a powerful and useful tool for eliciting a Th2-type-driven immune response, lending mechanistic insight into severe RSV infection. Here we present several materials and methods used for propagating and purifying RSV, infecting mice with RSV, and analyzing samples from RSV-infected mice.