Title : A subunit precision vaccine against sars-COV-2 mimicking the natural protective immunity
Abstract:
The high genetic variability of the new coronavirus SARS-CoV-2 that caused the ongoing severe acute respiratory syndrome related coronavirus 2 disease (COVID19) pandemic, is urging the development of precision vaccines. We herein, present the development of vaccine subunits that mimic the natural protective immunity elicited by structural regions of the virus associated with infective power. We have first identified using rational and computational approaches 14 potential epitopes located in a region involved in SAR-CoV-2 high infectivity. Hence, we engineered a series of polypeptides containing these epitopes. We developed an indirect ELISA assay and used it to show that the antibody response, to two polypeptides is highly associated to the asymptomatic and mild forms of the disease in a patients-centered study using a cohort of 500 SARS-CoV-2 COVID19 patients [p<0.001]. This association along with the neutralizing activity of these natural antibodies is in favor of a protective immunity. Furthermore, immunization of BALBc mice with these polypeptides, using various adjuvant, elicited strong humoral immune response. Upon these findings, we engineered different multivalent subunits from the sequences found to elicit a protective immune response. We showed that these engineered antigens elicit B and T cell immunity in patients with COVID19. Computational analysis tools showed that these subunits were structurally stable, antigenic and non-allergenic, thus suitable for human precision vaccination. Immunization of BALBc mice with recombinant forms of the engineered subunits using various adjuvants yielded strong long-lasting neutralizing specific antibodies. The approach represent a useful novel approach to design a precision vaccine to SARS-CoV-2 that can be applied to a number of highly pathogenic human viruses that can cause pandemics and for which no efficient precision vaccines are currently available.
