Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals
Author:
Lucas CarolinaORCID, Vogels Chantal B. F., Yildirim Inci, Rothman Jessica E., Lu Peiwen, Monteiro Valter, Gelhausen Jeff R., Campbell Melissa, Silva JulioORCID, Tabachikova Alexandra, Muenker M. Catherine, Breban Mallery I., Fauver Joseph R., Mohanty Subhasis, Huang Jiefang, Pearson Claire, Muyombwe Anthony, Downing Randy, Razeq Jafar, Petrone Mary, Ott Isabel, Watkins Anne, Kalinich Chaney, Alpert Tara, Brito Anderson, Earnest Rebecca, Murphy Steven, Neal Caleb, Laszlo Eva, Altajar Ahmad, Tikhonova Irina, Castaldi Christopher, Mane Shrikant, Bilguvar Kaya, Kerantzas Nicholas, Ferguson David, Schulz Wade, Landry Marie, Peaper David, Shaw Albert C., Ko Albert I., Omer Saad B., Grubaugh Nathan D., Iwasaki AkikoORCID,
Abstract
AbstractThe emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.
Publisher
Cold Spring Harbor Laboratory
Cited by
17 articles.
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