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. 2021 Sep 3;7(36):eabj5365.
doi: 10.1126/sciadv.abj5365. Epub 2021 Sep 3.

Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination

Affiliations

Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination

Tom G Caniels et al. Sci Adv. .

Abstract

Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.1.7, B.1.351, and P.1) in cohorts of COVID-19 convalescent patients (n = 69) and Pfizer-BioNTech vaccine recipients (n = 50). Spike binding and neutralization against all three VOCs were substantially reduced in most individuals, with the largest four- to sevenfold reduction in neutralization being observed against B.1.351. While hospitalized patients with COVID-19 and vaccinees maintained sufficient neutralizing titers against all three VOCs, 39% of nonhospitalized patients exhibited no detectable neutralization against B.1.351. Moreover, monoclonal neutralizing antibodies show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1 but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOCs and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOCs.

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Figures

Fig. 1.
Fig. 1.. Binding of convalescent and vaccinee sera to VOCs B.1.1.7, B.1.351, and P.1 spike proteins.
(A) Structural representation of spike (S) protein with its three domains (NTD, magenta; RBD, blue; S2 domain, green). Mutations in each of the VOC S proteins are listed and their location in the trimer. Colors correspond to the S protein domains in which the mutation occurs in. (B) Half-maximal binding (ED50) titers of polyclonal convalescent sera (left, n = 57) and vaccinee sera (right, n = 50) to S protein of B.1.1.7, B.1.351, and P.1 VOCs. Connected dots indicate results from the same individual. The lower cutoff for binding was set at an ED50 of 10 (gray shading). (C) Means ± SEM fold reductions in ED50 titers for convalescent patients and vaccine recipients against S proteins of B.1.1.7, B.1.351, and P.1 VOCs in comparison to ED50 titers to the wild-type (WT) S protein. (D) ED50 titers of nonhospitalized patients with COVID-19, hospitalized patients with COVID-19, and vaccine recipients against WT S protein and each of the VOC S protein. ****P < 0.0001 and ***P < 0.001; ns, not significant. All data points shown here represent the mean of a technical triplicate.
Fig. 2.
Fig. 2.. Neutralization of VOCs B.1.1.7, B.1.351, and P.1 by convalescent and vaccinee sera.
(A) Half-maximal neutralization (ID50) titers of polyclonal sera from nonhospitalized convalescent patients (n = 41), hospitalized convalescent patients (n = 28), and vaccine recipients (n = 50) against pseudoviruses of WT and B.1.1.7, B.1.351, and P.1 VOCs. Connected dots indicate results from the same individual. The lower cutoff for neutralization was set at an ID50 of 100 (gray shading). (B) Means ± SEM fold reductions in ID50 titers for nonhospitalized convalescent patients, hospitalized convalescent patients, and vaccine recipients against B.1.1.7, B.1.351, and P.1 VOCs pseudoviruses in comparison to ID50 titers against the WT pseudovirus. (C) Percentage of individuals in each of the three groups in (B) that has no detectable serum neutralizing activity (ID50 < 100) against the indicated pseudoviruses. (D) ID50 titers of nonhospitalized patients, hospitalized patients, and vaccine recipients against WT pseudovirus and each of the VOC pseudoviruses. ****P < 0.0001, ***P < 0.001, **P < 0.01, and *P < 0.05. All data points shown here represent the mean of a technical triplicate and are representative of at least two independent experiments.
Fig. 3.
Fig. 3.. Binding kinetics and neutralization of NAbs isolated from convalescent patients with COVID-19.
(A) BLI sensorgrams of 15 NAbs binding profile to WT spike and to each of the VOC S proteins (WT, gray; B.1.1.7, orange; B.1.351, purple; P.1, green). The dotted lines indicate the end of NAb association and the start of dissociation. (B) IC50 values of 15 NAbs to each of the pseudoviruses used in Fig. 2, separated by their target epitope on S protein. COVA1-18, COVA2-15, COVA2-17, and COVA1-16 are highlighted because of their neutralization characteristics. The gray shading indicates the maximum NAb concentration tested (50 μg/ml). Connected dots indicate IC50 values from the same NAb. Each dot represents the means ± SD of a technical triplicate. The curves shown are representative of at least two independent experiments.

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