PT  - JOURNAL ARTICLE
AU  - Yongjun Sui
AU  - Jianping Li
AU  - Hanne Andersen
AU  - Roushu Zhang
AU  - Sunaina Kiran Prabhu
AU  - Tanya Hoang
AU  - David Venzon
AU  - Anthony Cook
AU  - Renita Brown
AU  - Elyse Teow
AU  - Jason Velasco
AU  - Laurent Pessaint
AU  - Ian N. Moore
AU  - Laurel Lagenaur
AU  - Jim Talton
AU  - Matthew W. Breed
AU  - Josh Kramer
AU  - Kevin W. Bock
AU  - Mahnaz Minai
AU  - Bianca M. Nagata
AU  - Hyoyoung Choo-Wosoba
AU  - Mark G. Lewis
AU  - Lai-Xi Wang
AU  - Jay A. Berzofsky
TI  - An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques
AID  - 10.1101/2021.10.19.464990
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.19.464990
4099  - http://biorxiv.org/content/early/2021/10/20/2021.10.19.464990.short
4100  - http://biorxiv.org/content/early/2021/10/20/2021.10.19.464990.full
AB  - Emerging of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity poses threats to curbing the COVID-19 pandemic. An effective, safe, and convenient booster vaccine will be needed. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is hardest to cross-neutralize. Herein we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. One year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specifc CD4+ and CD8+ T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated one year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.Competing Interest StatementThe authors have declared no competing interest.