Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

Abstract

Beginning in late 2020, the emergence and spread of multiple variant SARS-CoV-2 strains harboring mutations which may enable immune escape necessitates the rapid evaluation of second generation COVID-19 vaccines, with the goal of inducing optimized immune responses that are broadly protective. Here we demonstrate in a mouse immunogenicity study that two doses of a modified B.1.351 spike (S)-Trimer vaccine (B.1.351 S-Trimer) candidate can induce strong humoral immune responses that can broadly neutralize both the original SARS-CoV-2 strain (Wuhan-Hu-1) and Variants of Concern (VOCs), including the UK variant (B.1.1.7), South African variant (B.1.351) and Brazil variant (P.1). Furthermore, while immunization with two doses (prime-boost) of Prototype S-Trimer vaccine (based on the original SARS-CoV-2 strain) induced lower levels of cross-reactive neutralization against the B.1.351 variant, a third dose (booster) administered with either Prototype S-Trimer or B.1.351 S-Trimer was able to increase neutralizing antibody titers against B.1.351 to levels comparable to neutralizing antibody titers against the original strain elicited by two doses of Prototype S-Trimer.

Antibody longevity and cross-neutralizing activity following SARS-CoV-2 wave 1 and B.1.1.7 infections

“…Spikes from VOCs are being investigated as second-generation vaccine candidates to tackle the challenges associated with protection against SARS-CoV-2 emerging variants [34][35][36][37] and therefore, studying the immune response to Spike variants in natural infection can provide insight into differential Spike immunogenicity. We show that infection with B.1.1.7 elicits a robust neutralizing antibody response against B.1.1.7, P.1 and WT variants.…”

“…To counter such mutations and their attendant antigenic changes, vaccines using the Spike proteins from these variants of concern (VOCs) are under investigation. [34][35][36][37] Whether the variant Spikes will elicit a robust neutralizing response with superior cross-neutralizing activity against parental strains and newly emerging variants has not been extensively studied. 26,38,39 Natural infection provides an important opportunity to compare the neutralizing antibody titres and cross-neutralizing activity generated from individuals exposed to different Spike variants and will give insights into how mutations in Spike impact immunogenicity, thereby informing the design of second generation vaccine candidates based on VOCs.…”

Immunogenicity of SARS-CoV-2 trimetric spike protein associated to Poly(I:C) plus Alum

“…All rights reserved. No reuse allowed without permission.The copyright holder for this preprint this version posted October 6, 2021. ; https://doi.org/10.1101/2021.10.05.461434 doi: bioRxiv preprint adjuvant CpG + Alum coupled activity in some cases(53)(54)(55). Poly(I:C) is a TLR3 agonist and formulations of mixed adjuvant containing Alum + Poly(I:C) have been shown to elicit a T cell immune response.…”

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2

“…The vaccines specifically targeted at the Beta (B.1.351) SARS-CoV-2 variant has recently begun to be developed, and the anti-Beta (B.1.351) vaccine candidate has been tested in combination with the prototype as a bivalent vaccine or as a heterologous prime boost 26,27 . Here, we provided another novel strategy for the construction of a vaccine with broad neutralization capability, which incorporated different variant-specific antigens into a single hybrid immunogen.…”