Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Induced by Natural Infection or Vaccination: A Systematic Review and Pooled Analysis

Abstract

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection-mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6-4.7-fold), 1.8-fold (1.4-2.4-fold), and 3.2-fold (2.4-4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2-1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5-9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7-4.4-fold) for messenger RNA platform, and 2.5-fold (1.7-2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.

Keywords: SARS-CoV-2 variants; natural infection; neutralizing antibodies; vaccination.

Figure 1.

Selection flowchart of studies, study participants, and variants studied. Abbreviations: mRNA, messenger RNA; VSV, vesicular stomatitis virus.

Figure 2.

Neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 variants in non–variant-infected individuals. Neutralizing antibodies against reference strains (gray dots), variants of concern (red dots), variants of interest (blue dots), and alerts for further monitoring (green dots) were determined with live virus neutralization assay (A), lentivirus-vector pseudovirus neutralization assay (B), and vesicular stomatitis virus (VSV)–vector pseudovirus neutralization assay (C). Solid points represent geometric mean titers (GMTs); error bars, 95% confidence intervals; scattering dots, individual titers; numbers in orange rectangle, number of studies and sample size (no. of studies/no. of samples). *P ≤.05; **P ≤.01; ***P ≤.001. Abbreviation: Pango, Phylogenetic Assignment of Named Global Outbreak.

Figure 3.

Neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in uninfected vaccine recipients after administration of different vaccine platforms. Neutralizing antibodies against reference strains (gray dots), variants of concern (red dots), variants of interest (blue dots), and alerts for further monitoring (green dots) were determined with live virus neutralization assay (A), lentivirus-vector pseudovirus neutralization assay (B), and vesicular stomatitis virus (VSV)–vector pseudovirus neutralization assay (C). Solid points represent geometric mean titers (GMTs); error bars, 95% confidence intervals; scattering dots, individual titers; and numbers in the orange rectangles, number of studies and sample size (no. of studies/no. of samples). *P ≤.05; **P ≤.01; ***P ≤.001. Abbreviations: mRNA, messenger RNA; Pango, Phylogenetic Assignment of Named Global Outbreak.

Figure 4.

Comparison between geometric mean titers (GMTs) of neutralizing antibodies induced by natural infection and vaccination by platforms. Neutralizing antibodies comparison were determined in live virus neutralization assay (A), lentivirus-vector pseudovirus neutralization assay (B), and vesicular stomatitis virus (VSV)–vector pseudovirus neutralization assay (C). Neutralization against the same lineage induced by natural infection and different platforms of vaccination was compared. Solid points represent GMTs; error bars, 95% confidence intervals; scattering dots, individual titers; and numbers in orange rectangles, number of studies and sample size (no. of studies/no. of samples). *P ≤.05; **P ≤.01; ***P ≤.001. Abbreviations: mRNA, messenger RNA; NR, nonreplicating.