Cell Rep. https://doi.org/10.1016/j.celrep.2021.109452 (2021)

Intranasal vaccination can have several advantages over conventional intramuscular vaccines, not least because they can generate strong immune responses at key sites of pathogen exposure such as the lungs. In Cell Reports, Diamond and colleagues use a chimpanzee adenoviral-vectorized vaccine that expresses the CoV-2 spike protein (ChAd-SARS-CoV-2-S) and investigate the durability, dose response and cross-protective effects in humanized mice after intranasal administration. A single intranasal dose of vaccine induced humoral responses that were superior to the intramuscular route both in terms of antibody titer and neutralizing efficacy. Intranasal vaccine also generated long-lived plasma cells in the bone marrow that were absent or minimally present with intramuscular dosing. Notably, intranasal vaccination protected against variants of concern such as B.1.351 (Beta) for up to 9 months.