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Neutralizing Antibodies Against SARS-CoV-2 Variants Induced by Natural Infection or Vaccination: A Systematic Review and Individual Data Meta-Analysis
104 Pages Posted: 2 Jun 2021
More...Abstract
Background: Recently emerged SARS-CoV-2 variants may pose a threat to immunity derived from prototypical SARS-CoV-2 infection or vaccination. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed.
Methods: We systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. Through pooled analyses we estimated lineage-specific GMTs across different study participants and types of neutralization assays.
Findings: We identified 76 studies, including 2,876 individuals and 10,526 neutralization tests, meeting the eligibility criteria. Compared with reference lineage B, B.1.351 and B.1.617 significantly escaped natural-infection-mediated neutralization, with an average of 3.8-fold (95% CI: 3.4-4.4) and 4.0-fold (95% CI: 2.3-6.9) reduction in live virus neutralization assay, while neutralizing antibody titers against B.1.1.7 decreased slightly (1.3-fold, 95%CI: 1.1-1.6). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 and B.1.617, with a 32.6-fold (95% CI: 18.7-56.9) and 11.4-fold (95% CI: 8.6-15.2) for non-replicating vector vaccines, while 4.4-fold (95% CI: 4.0-5.0) and 2.1-fold (95%CI: 1.6-2.8) for mRNA platform vaccine. Neutralizing antibodies levels induced mRNA vaccines against SARS-CoV-2 variants were similar, or higher, than that derived from naturally-infected individuals.
Interpretation: Antibody responses established by natural infection or vaccination have similar ability to neutralize B.1.1.7, but neutralizing titers against B.1.351 and B.1.617 were significantly reduced. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed.
Registration Information: The study has been registered with PROSPERO and is awaiting approval (ID: 256932).
Funding Information: This study was funded by the National Science Fund for Distinguished Young Scholars (grant no. 81525023), Program of Shanghai Academic/Technology Research Leader (grant no.18XD1400300), National Science and Technology Major project of China (grant no. 2018ZX10713001-007, 2017ZX10103009-005, 2018ZX10201001-010), the US National Institutes of Health (R01 AI135115 to D.T.L. and A.S.A.)
Declaration of Interests: H.Y. has received research funding from Sanofi Pasteur, and Shanghai Roche Pharmaceutical Company; D.T.L. and A.S.A. has received research funding from the US National Institutes of Health. None of those research funding is related to COVID-19. All other authors report no competing interests.
Keywords: SARS-CoV-2 variants; neutralizing antibodies; natural infection; vaccination
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