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Pre-Clinical Testing of Two Serologically Distinct Chimpanzee-Origin Adenovirus Vectors Expressing Spike of SARS-CoV-2
24 Pages Posted: 16 Mar 2022
More...Abstract
Two serologically distinct chimpanzee-origin, replication-defective adenovirus (AdC) vectors expressing the spike (S) protein of an early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate were generated and tested for induction of antibodies in young and aged mice. Both vectors induced S protein-specific antibodies including neutralizing antibodies. Levels of antibodies increased after a boost. The effectiveness of the boost depended on vector dose and timing between the two immunizations. Using two heterologous AdC vectors was more effective than vaccinating with the same vector repeatedly. Antibodies partially cross-reacted between different S protein variants. Cross-reactivity increased after booster immunization with vectors carrying the same S gene, expression of two different S proteins by the AdC vectors used for the prime and the boost did not selectively increase responses against the variants.
Funding Information: This work was funded by grants from The G. Harold and Leila Y. Mathers Charitable Foundation, the Commonwealth of Pennsylvania, and the Wistar Science Discovery Fund. MH was the recipient from the Fellowship from Janssen Scientific Affairs. Support for Shared Resources utilized in this study was provided by Cancer Center Support Grant (CCSG) P30CA010815 to The Wistar Institute.
Declaration of Interests: HCJE holds equity in Virion Therapeutics. She serves as a Consultant to several Gene Therapy companies.
Ethics Approval Statement: Female C57Bl/6 mice (6–8 weeks of age) were purchased from the Jackson Laboratories (Bar Harbor, ME). Outbred 6–8-week-old female ICR mice were obtained from Taconic Biosciences (New York, NY). Mice were housed at the Wistar Institute Animal Facility. All mouse procedures followed approved protocols.
Keywords: Vaccine, SARS-CoV-2, spike protein, antibody responses, prime boost regimens
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