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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

See all articles by Mikhail Novikov

Mikhail Novikov

affiliation not provided to SSRN

Mohadeseh Hasanpourghadi

affiliation not provided to SSRN

Robert Ambrose

affiliation not provided to SSRN

Arezki Chekaoui

affiliation not provided to SSRN

Dakota Newman

affiliation not provided to SSRN

Wynetta Giles-Davis

affiliation not provided to SSRN

Zhiquan Xiang

affiliation not provided to SSRN

Xiangyang Zhou

affiliation not provided to SSRN

Hildegund C. J. Ertl

Wistar Institute

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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

Suggested Citation

Novikov, Mikhail and Hasanpourghadi, Mohadeseh and Ambrose, Robert and Chekaoui, Arezki and Newman, Dakota and Giles-Davis, Wynetta and Xiang, Zhiquan and Zhou, Xiangyang and Ertl, Hildegund C. J., Pre-Clinical Testing of Two Serologically Distinct Chimpanzee-Origin Adenovirus Vectors Expressing Spike of SARS-CoV-2. Available at SSRN: https://ssrn.com/abstract=4059223 or http://dx.doi.org/10.2139/ssrn.4059223

Mikhail Novikov

affiliation not provided to SSRN ( email )

No Address Available

Mohadeseh Hasanpourghadi

affiliation not provided to SSRN ( email )

No Address Available

Robert Ambrose

affiliation not provided to SSRN ( email )

No Address Available

Arezki Chekaoui

affiliation not provided to SSRN ( email )

No Address Available

Dakota Newman

affiliation not provided to SSRN ( email )

No Address Available

Wynetta Giles-Davis

affiliation not provided to SSRN ( email )

No Address Available

Zhiquan Xiang

affiliation not provided to SSRN ( email )

No Address Available

Xiangyang Zhou

affiliation not provided to SSRN ( email )

No Address Available

Hildegund C. J. Ertl (Contact Author)

Wistar Institute ( email )

United States