Currently approved SARS-CoV-2 vaccines induce robust systemic immunity but poor immunity at the respiratory mucosa, meaning that they are highly effective against symptomatic disease but do not prevent viral transmission. In Science, Mao et al. developed a vaccine strategy that induced mucosal immune memory within the respiratory tract and reduced viral transmission. K18-hACE2 mice were vaccinated with mRNA-LNP (Pfizer/BioNTech BNT162b2) by intramuscular injection, and 14 days later unadjuvanted spike protein was administered intranasally; termed the ‘prime and spike regimen’. This resulted in high levels of anti-SARS-CoV-2 IgA and IgG in the nasal wash and bronchoalveolar lavage fluid (BALF), and the accumulation of spike-specific CD8 T cells and antigen-experienced CD4 T cells in the lung and BALF. The prime and spike regimen provided protection from COVID-19-like disease after challenge with a lethal SARS-CoV-2 infection and reduced viral transmission in a hamster model of SARS-CoV-2. Thus, a prime and spike regimen induces a protective mucosal immune response and reduces the transmission of SARS-CoV-2.

Original reference: Science (2022)