Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

Abstract

Both natural infection with SARS-CoV-2 and immunization with vaccines induce protective immunity. However, the extent to which such immune responses protect against emerging variants is of increasing importance. Such variants of concern (VOC) include isolates of lineage B.1.1.7, first identified in the UK, and B.1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417, escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks of the receptor-binding domain. To address the potential threat posed by VOC, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort sampled in the early convalescent stages after natural infection in the first wave of the pandemic in Spring 2020. We tested antibody and T cell responses against a reference isolate of the original circulating lineage, B, and the impact of sequence variation in the B.1.1.7 and B.1.351 VOC. Neutralization of the VOC compared to B isolate was reduced, and this was most evident for the B.1.351 isolate. This reduction in antibody neutralization was less marked in post-boost vaccine-induced responses compared to naturally induced immune responses and could be largely explained by the potency of the homotypic antibody response. After a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOC was completely abrogated in the majority of vaccinees. Importantly, high magnitude T cell responses were generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. These data indicate that VOC may evade protective neutralizing responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine dose, but the impact of the VOC on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants.

Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals

“…The present study did not assess decreases in antibody reactivity, as several other studies have already investigated this matter. 11,[14][15][16][17][18][19][20]22,23 Our studies used overlapping peptide pools. As such, we cannot exclude that some of the mutations may involve alterations in terms of antigen processing for either class I or class II, which would be undetected by using pools of ''preprocessed'' peptides.…”

“…Numerous reports address the effect of variant spike (S) mutations on antibody binding and function. 11,[14][15][16][17][18][19][20][21][22][23] In general, the impact of B.1.1.7 mutations on neutralizing antibody titers is moderate. [15][16][17][18]20,24 In contrast, mutations in B.1.351 and P.1 variants are associated with the more pronounced loss of neutralizing capacity.…”

“…11,[14][15][16][17][18][19][20][21][22][23] In general, the impact of B.1.1.7 mutations on neutralizing antibody titers is moderate. [15][16][17][18]20,24 In contrast, mutations in B.1.351 and P.1 variants are associated with the more pronounced loss of neutralizing capacity. 15,16,22,23,25 Concerning vaccination responses, the AstraZeneca ChAdOx1 vaccine has been associated with a partial loss of neutralizing antibody activity against B.1.1.7 15 and a large loss of neutralizing activity against B.1.351.…”

“…[15][16][17][18]20,24 In contrast, mutations in B.1.351 and P.1 variants are associated with the more pronounced loss of neutralizing capacity. 15,16,22,23,25 Concerning vaccination responses, the AstraZeneca ChAdOx1 vaccine has been associated with a partial loss of neutralizing antibody activity against B.1.1.7 15 and a large loss of neutralizing activity against B.1.351. 26 ChAdOx1 maintains efficacy against B.1.1.7 24,27 but has a major loss in efficacy against mild COVID-19 with the B.1.351 variant.…”

Differences in the concentration of anti-SARS-CoV-2 IgG antibodies post-COVID-19 recovery or post-vaccination

“…Moreover, studies by Angyal et al[22] showed that the rst administration of the vaccine strengthens the cellular response, as well as in vitro it strengthens the neutralizing properties in relation to the variant B.1.351 (South African). This aspect is pointed out by Skelly et al [33], who tested the neutralization strength of antibodies resulting from natural SARS-CoV-2 infection and immunization with the P zer/BioNTech vaccine. They noted that there is a difference in the humoral (decreased neuralization) and, to a lesser extent, cellular responses to variants of the B1.1.7 (UK) and B1.351 lines.…”