Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, Beta, Delta, and Omicron variants

Med (N Y). 2022 Jun 10;3(6):422-432.e3. doi: 10.1016/j.medj.2022.04.002. Epub 2022 Apr 14.


Background: SARS-CoV-2 Omicron variant of concern (VOC) has evolved multiple mutations within the spike protein, raising concerns of increased antibody evasion. In this study, we assessed the neutralization potential of COVID-19 convalescent sera and sera from vaccinated individuals against ancestral SARS-CoV-2 and VOCs.

Methods: The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2 and Beta, Delta, and Omicron VOCs was assessed using a micro-neutralization assay.

Findings: Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against Beta and Omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the Omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the Delta variant, was not sufficient to induce high neutralizing antibody titers against Omicron.

Conclusions: In summary, we demonstrate that convalescent and vaccinated sera display varying levels of SARS-CoV-2 VOC neutralization. Data from this study will inform booster vaccination strategies against SARS-CoV-2 VOCs.

Funding: This research was funded by the Canadian Institutes of Health Research (CIHR). VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility.

Keywords: Delta; Omicron; SARS-CoV-2; convalescent; long-term; microneutralization; neutralization; neutralizing antibodies; vaccine; variants of concern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Serotherapy
  • COVID-19* / prevention & control
  • COVID-19* / therapy
  • Humans
  • Immunization, Passive
  • Membrane Glycoproteins / genetics
  • Neutralization Tests
  • SARS-CoV-2 / genetics
  • Saskatchewan
  • Spike Glycoprotein, Coronavirus* / genetics
  • Viral Envelope Proteins / genetics


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants