An AAV-based, room-temperature stable, single dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates

Zabaleta, Nerea; Dai, Wenlong; Bhatt, Urja; Hérate, Cécile; Maisonnasse, Pauline; Chichester, Jessica A.; Sanmiguel, Julio; Estelien, Reynette; Michalson, Kristofer T.; Diop, Cheikh; Maciorowski, Dawid; Dereuddre-Bosquet, Nathalie; Cavarelli, Mariangela; Gallouët, Anne-Sophie; Naninck, Thibaut; Kahlaoui, Nidhal; Lemaitre, Julien; Qi, Wenbin; Hudspeth, Elissa; Cucalon, Allison; Dyer, Cecilia D.; Pampena, M. Betina; Knox, James J.; LaRocque, Regina C.; Charles, Richelle C.; Li, Dan; Kim, Maya; Sheridan, Abigail; Storm, Nadia; Johnson, Rebecca I.; Feldman, Jared; Hauser, Blake M.; Contreras, Vanessa; Marlin, Romain; Tsong Fang, Raphaël Ho; Chapon, Catherine; van der Werf, Sylvie; Zinn, Eric; Ryan, Aisling; Kobayashi, Dione T.; Chauhan, Ruchi; McGlynn, Marion; Ryan, Edward T.; Schmidt, Aaron G.; Price, Brian; Honko, Anna; Griffiths, Anthony; Yaghmour, Sam; Hodge, Robert; Betts, Michael R.; Freeman, Mason W.; Wilson, James M.; Le Grand, Roger; Vandenberghe, Luk H.

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and are easily delivered. Here, AAVCOVID-1, an adeno-associated viral (AAV), Spike gene-based vaccine candidate demonstrates potent immunogenicity in mouse and nonhuman primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T-cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans, does not elicit cross-reactivity to common AAVs used in gene therapy, and its persistence and expression wanes following injection. The single, low dose requirement, high yield manufacturability, and 1-month stability for storage at room-temperature may make this technology well-suited to support effective immunization campaigns for emerging pathogens on a global scale.