Professor Abhi Singharoy
School of Molecular Sciences
Arizona State University
Tempe, AZ
Webinar link below or attend in person in Beckman - Room 3269

Monday, September 20, 2021
3:00 pm (CT)
Hybrid webinar recording

Abstract

Viral vectored platforms such as AstraZenaca (AZD) and J&J's vaccines, have shown efficacy of 62-92% infection reduction and 100% efficacy in preventing the spread of COVID. These established Adenovirus technologies are amenable to rapid mass-production with favorable storage conditions. They also have higher potential to induce robust T-cell immunity, and therefore generate longer lasting immunogenicity than the mRNA interventions. Despite these successes, two side-effects arise: (i) once an AZD or J&J vaccine administered, future attempts at delivering therapy with the same vector will likely be rendered ineffectual, affecting the immediate dissemination of booster doses to the patient population, and (ii) the vector-based vaccines are implicated in blood clotting in a small, yet significant, number of patients. With cryo-EM experiments and molecular dynamics flexible fitting refinement, we have resolved the first near-atomic model of the AZD's ChAdOx vaccine (popularly called the 'Oxford Vaccine') at 3.3 Å, and that of the J&J's Ad26- based vaccine [1]. Using ARBD simulations and surface plasmon resonance experiments, we discovered a potential mechanism of blood- clotting in both these vaccine candidates, allowing us now to re- designed the AZD vaccine on an industrial scale. To reduce patient mortality, we have ranked countries by their COVID risk [2], and are computationally engineering ChAdOx and Ad26 epitopes to conceive nationality-specific booster doses of the original AZD or J&J vector. 1.https://www.biorxiv.org/content/biorxiv/early/2021/05/24/2021.05.1 9.444882.full.pdf 2.https://www.sciencedirect.com/science/article/pii/S266637912100037 9