An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission

Abstract

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.

Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques

“…IgA is known to be a potent neutralizer 35-37 and a strong driver of opsinophagocytic function 38 . Due to its polyfunctionality and mucosal localization, vaccine formulations and platforms have sought to enhance IgA responses 34,39-42 . Our study supports the notion that vaccine delivery route can greatly impact mucosal IgA induction.…”

Quantifying the effect of vaccination on transmission in modelling studies

“…Making a vaccine that can reduce viral emissions would require significant time, resources and perhaps administration directly into the upper respiratory tract, rather than the intramuscular route. 5 However, successful development and stockpiling of such a vaccine could be major breakthrough for not only SARS-CoV-2, but also for future coronavirus pandemics. We would be greatly interested to see the effects of a vaccine that could reduce transmission within the model of this paper by decreasing viral emissions from an infected host; such a model would justify even more the development of a pan-coronavirus vaccine as well as the specific investigation of transmission as a clinical outcome in future vaccine development.…”