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. 2022 Apr 20;14(641):eabn6150.
doi: 10.1126/scitranslmed.abn6150. Epub 2022 Apr 20.

Characterization of immune responses in fully vaccinated individuals after breakthrough infection with the SARS-CoV-2 delta variant

Ai-Ris Y Collier  1   2   3 , Catherine M Brown  4 , Katherine A McMahan  1 , Jingyou Yu  1 , Jinyan Liu  1 , Catherine Jacob-Dolan  1   2 , Abishek Chandrashekar  1 , Dylan Tierney  4 , Jessica L Ansel  1 , Marjorie Rowe  1 , Daniel Sellers  1 , Kunza Ahmad  1 , Ricardo Aguayo  1   3 , Tochi Anioke  1 , Sarah Gardner  1 , Mazuba Siamatu  1 , Lorraine Bermudez-Rivera  1 , Michele R Hacker  2   3 , Lawrence C Madoff  4 , Dan H Barouch  1   2   5
Affiliations

Characterization of immune responses in fully vaccinated individuals after breakthrough infection with the SARS-CoV-2 delta variant

Ai-Ris Y Collier et al. Sci Transl Med. .

Abstract

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported frequently in vaccinated individuals with waning immunity. In particular, a cluster of over 1000 infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. In this study, vaccinated individuals who tested positive for SARS-CoV-2 (n = 16) demonstrated substantially higher serum antibody responses than vaccinated individuals who tested negative for SARS-CoV-2 (n = 23), including 32-fold higher binding antibody titers and 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed higher mucosal antibody responses in nasal secretions and higher spike protein-specific CD8+ T cell responses in peripheral blood than did vaccinated individuals who tested negative. These data demonstrate that fully vaccinated individuals developed robust anamnestic antibody and T cell responses after infection with the SARS-CoV-2 delta variant. Moreover, these findings suggest that population immunity will likely increase over time by a combination of widespread vaccination and breakthrough infections.

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Figures

Fig. 1.
Fig. 1.. Antibody responses in COVID-19 distinguish vaccinated individuals with and without confirmed SARS-CoV-2 breakthrough infection.
Serum antibody responses were measured in individuals who received BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines as part of the SARS-CoV-2 outbreak investigation in Provincetown, Massachusetts. Vaccinated uninfected (open circles) and vaccinated infected (filled circles) individuals are shown. (A and B) IgG binding antibody titers by multiplexed electrochemiluminescence (ECLA) assays against SARS-CoV-2 Spike protein from WA1/2020, B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.617.1 (kappa) variants (A) and against the non-vaccine antigen Nucleocapsid (Nuc) in (B) are displayed in relative light units (RLU). (C) Serum IgG titers to SARS-COV-2 receptor binding domain (RBD) variants were measured by ELISA. (D) Pseudovirus neutralizing antibody (NAb) titers were measured in serum samples as 50% reduction (NT50) of luciferase expression. Medians (red bar) are displayed below the x-axis. Dotted horizontal lines indicate limit of detection. P values (Wilcoxon rank-sum test) compare each Spike protein variant or Nucleocapsid between uninfected and infected participants.
Fig. 2.
Fig. 2.. T cell responses are enhanced in COVID-19 vaccinated individuals with confirmed SARS-CoV-2 breakthrough infection compared to those without infection.
(A and B) Intracellular cytokine staining assays were used to measure percent IFN-γ production in CD4+ T cells (A) and CD8+ T cells (B) in response to pooled Spike peptides. Vaccinated uninfected (open circles) and vaccinated infected (filled circles) individuals are shown. Assays were conducted using pooled Spike peptides from WA1/2020 or B.1.617.2 (delta). Medians (red bar) for each variant are displayed below the x-axis. Dotted horizontal lines indicates lower limit of quantitation. P values reflect Wilcoxon rank-sum tests.
Fig. 3.
Fig. 3.. Mucosal RBD-specific nasal swab IgA and IgG responses are increased following breakthrough infection after COVID-19 vaccination compared to uninfected, vaccinated individuals.
(A and B) SARS-CoV-2 RBD-specific IgA (A) and IgG (B) responses in nasal swabs were measured by ELISA. Vaccinated uninfected (open circles) and vaccinated infected (filled circles) individuals are shown. Nasal ELISA titers are shown against WA1/2020 and B.1.617.2 (delta) variant RBD proteins. Medians (red bar) for each variant are displayed below the x-axis. Dotted horizontal lines indicate limit of detection. P values reflect Wilcoxon rank-sum tests.
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