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

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.