Relevance of immune response and vaccination strategies of SARS-CoV-2 in the phase of viral red queen dynamics

Abstract

Background: Following a relatively mild first wave of coronavirus disease 2019 (COVID-19) in India, a deadly second wave of the pandemic overwhelmed the healthcare system due to the emergence of fast-transmitting SARS-CoV-2 genetic variants. The emergence and spread of the B.1.617.2/Delta variant considered to be driving the devastating second wave of COVID-19 in India. Currently, the Delta variant has rapidly overtaken the previously circulating variants to become the dominant strain. Critical mutations in the spike/RBD region of these variants have raised serious concerns about the virus's increased transmissibility and decreased vaccine effectiveness. As a result, significant scientific and public concern has been expressed about the impact of virus variants on COVID-19 vaccines.

Objectives: The purpose of this article is to provide an additional explanation in the context of the evolutionary trajectory of SARS-CoV-2 variants in India, the vaccine-induced immune response to the variants of concern (VOC), and various vaccine deployment strategies to rapidly increase population immunity.

Content: Phylogenetic analysis of SARS-CoV-2 isolates circulating in India suggests the emergence and spread of B.1.617 variant. The immunogenicity of currently approved vaccines indicates that the majority of vaccines elicit an antibody response and some level of protection. According to current data, vaccines in the pre-fusion configuration (2p substitution) have an advantage in terms of nAb titer, but the duration of vaccine-induced immunity, as well as the role of T cells and memory B cells in protection, remain unknown. Since vaccine efficacy on virus variants is one of the major factors to be considered for achieving herd immunity, existing vaccines need to be improved or effective next-generation vaccines should be developed to cover the new variants of the virus.

Keywords: B.1.617; COVID-19; SARS-CoV-2; Variants.

Fig. 1

Evolution and lineage distribution of SARS-CoV-2 genomes across India (February 2020 – June 2021). (a) Temporal and spatial distributions of SARS-CoV-2 lineages in India depict the emergence and extinction of lineages over time. Lineage-wise breakdown of Indian genomes suggests the dominance of ancestral lineages (D614 & G614) during the first 6–8 months while these lineages were replaced by novel variants (B.1.36.29, B.1.1.7, B.1.351, B.1.617) during the latter half. (b) Maximum Likelihood (ML) phylogenetic tree inferred from 318 representative SARS-CoV-2 genomes from India shows the evolutionary divergence of the virus. Major lineages have been simplified as colored cartoon triangles using FigTree http://tree.bio.ed.ac.uk/software/figtree/ (c) Phylogenetic tree of the B.1.617 variant emerging in India (n ​= ​124) illustrates the three B.1.617 sub-lineages. All genome sequences were downloaded from GISAID (https://gisaid.org) and lineages were assigned using PANGOLIN v3.0 (https://pangolin.cog-uk.io/). The phylogenetic tree was constructed using multiple genome sequence alignment (MAFFT) by mapping against the Wuhan-Hu-1 strain (Accession: MN908947.3). ML tree was generated using IQTREE v.1.6.1 (http://www.iqtree.org/) under the GTR nucleotide substitution model with 1000 bootstrap replicates.

Fig. 2

Schematic representation of major mutations that characterize SARS-CoV-2 variants are illustrated. Mutations in receptor-binding motif ​(RBM) are colored in yellow, RBD in Cyan and S1, S2 regions are in blue.