Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge.
Author
Wong, Ting YLee, Katherine S
Russ, Brynnan P
Horspool, Alexander M
Kang, Jason
Winters, Michael T
Allison Wolf, M
Rader, Nathaniel A
Miller, Olivia A
Shiflett, Morgane
Izac, Jerilyn
Varisco, David
Sen-Kilic, Emel
Cunningham, Casey
Cooper, Melissa
Cyphert, Holly A
Barbier, Mariette
Martinez, Ivan
Bevere, Justin R
Ernst, Robert K
Damron, F Heath
Date
2022-03-14Journal
NPJ VaccinesPublisher
Springer NatureType
Article
Metadata
Show full item recordAbstract
SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®). The vaccine is adjuvanted with Bacterial Enzymatic Combinatorial Chemistry (BECC), BECC470. Intranasal (IN) administration of BreC-CoV-2 in K18-hACE2 mice induced a strong systemic and localized immune response in the respiratory tissues which provided protection against the Washington strain of SARS-CoV-2. Protection provided after IN administration of BReC-CoV-2 was associated with decreased viral RNA copies in the lung, robust RBD IgA titers in the lung and nasal wash, and induction of broadly neutralizing antibodies in the serum. We also observed that BReC-CoV-2 vaccination administered using an intramuscular (IM) prime and IN boost protected mice from a lethal challenge dose of the Delta variant of SARS-CoV-2. IN administration of BReC-CoV-2 provided better protection than IM only administration to mice against lethal challenge dose of SARS-CoV-2. These data suggest that the IN route of vaccination induces localized immune responses that can better protect against SARS-CoV-2 than the IM route in the upper respiratory tract.Rights/Terms
© 2022. The Author(s).Identifier to cite or link to this item
http://hdl.handle.net/10713/18343ae974a485f413a2113503eed53cd6c53
10.1038/s41541-022-00451-7