One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects non-human primates from SARS-CoV-2

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 (RSV) 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 immunity in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against two virus variants of concern. 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 a single-dose intranasal COVID-19 vaccine.

Respiratory Syncytial Virus Fusion Protein-encoding DNA Vaccine Is Less Effective in Conferring Protection against Inflammatory Disease than a Virus-like Particle Platform

Formalin-inactivated respiratory syncytial virus (RSV) vaccination causes vaccine-enhanced disease (VED) after RSV infection. It is considered that vaccine platforms enabling endogenous synthesis of RSV immunogens would induce favorable immune responses than non-replicating subunit vaccines in avoiding VED. Here, we investigated the immunogenicity, protection, and disease in mice after vaccination with RSV fusion protein (F) encoding plasmid DNA (F-DNA) or virus-like particles presenting RSV F (F-VLP). F-DNA vaccination induced CD8 T cells and RSV neutralizing Abs, whereas F-VLP elicited higher levels of IgG2a isotype and neutralizing Abs, and germinal center B cells, contributing to protection by controlling lung viral loads after RSV challenge. However, mice that were immunized with F-DNA displayed weight loss and pulmonary histopathology, and induced F specific CD8 T cell responses and recruitment of monocytes and plasmacytoid dendritic cells into the lungs. These innate immune parameters, RSV disease, and pulmonary histopathology were lower in mice that were immunized with F-VLP after challenge. This study provides important insight into developing effective and safe RSV vaccines.