Functional Analysis of Spike from SARS-CoV-2 Variants Reveals the Role of Distinct Mutations in Neutralization Potential and Viral Infectivity

Alona Kuzmina, Seraj Wattad, Stanislav Engel, Elli Rosenberg, Ran Taube

Research output: Contribution to journalArticlepeer-review

Abstract

Enhanced viral transmission and escape from vaccine–elicited neutralizing antibodies drive worldwide spread of SARS-CoV-2 variants and promote disease progression. However, the impact of specific spike mutations that are carried by different viral variants on viral infectivity and neutralization sensitivity has not been completely defined. Here, we use pseudoviruses to assess the contribution of spike mutations within the Receptor Binding Domain (RBD) and the Furin Cleavage Site (FCS), and appear in circulating viral variants, on viral infectivity and neutralization potential against sera that was drawn from fully vaccinated individuals. Our functional analysis demonstrates that single, P681H, P681R or A701V–FCS mutations do not play a role in viral infectivity and neutralization potential. However, when in conjunction with the RBD–N501Y mutation, viral infectivity is enhanced. Similarly, combining the E484K–RBD mutation to the spike that carries FCS mutations reduces neutralization sensitivity with no effects on viral infectivity. Employing a similar approach onto the spike from Delta or Lota SARS-CoV-2 variants further reveals that specific RBD mutations affect neutralization sensitivity or viral infectivity differently. Our results validate the efficacy of the Pfizer third dose vaccine against Delta and Lota SARS-CoV-2 variants, and outline the significance of distinct RBD mutations in promoting viral infectivity and neutralization sensitivity to post–vaccination sera.

Original languageEnglish
Article number803
Number of pages1
JournalViruses
Volume14
Issue number4
DOIs
StatePublished - 13 Apr 2022

Keywords

  • COVID-19
  • Delta
  • furin–cleavage site
  • Lota
  • neutralization antibodies
  • Pfizer–BTN162b2 vaccine
  • Receptor Binding Domain (RBD)
  • SARS-CoV-2
  • SARS-CoV-2 variants
  • spike

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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