Some of you may remember that I have complained about reports that Covid-19 vaccines may be less effective against the various new mutations (variants) of SARS-CoV-2 that have recently appeared. All these reports focused only on neutralizing antibodies (products of B cells) and said nothing about T cell immunity. Antibody studies are easy to do, but studies of T cell immunity are much more difficult and slower to do. Here is some good news on that subject!
Only the effects of the Moderna and Pfizer Covid-19 vaccines were studied in this paper, but it's known that the AstraZeneca (Oxford) and the Johnson & Johnson (Janssen) vaccines also develop potent T cell responses. It's reasonable to believe that they also might not be less effective against the new mutant strains of SARS-CoV-2. That research is probably in progress now.
Two of the authors, Shane Crotty and Alessandro Sette are at the U. of California San Diego and the La Jolla Institute for Immunology. They are well-known T cell experts.
I've pasted in the Summary and the Introduction sections from this article. And I've marked in bold the sentences I think are important for readers. If you don't understand the author's language, just ask. I'll try to answer.
Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees [people who were vaccinated].
AUTHORS
Alison Tarke1,2, John Sidney1, Nils Methot1, Yun Zhang4, Jennifer M. Dan1,3, Benjamin Goodwin1, Paul Rubiro1, Aaron Sutherland1, Ricardo da Silva Antunes1, April Frazier1, Stephen A. Rawlings3, Davey M. Smith3, Bjoern Peters,1,3, Richard H. Scheuermann1,4,5, Daniela Weiskopf1, Shane Crotty 1,3, Alba Grifoni1*, Alessandro Sette
Summary
The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity.
Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.
INTRODUCTION
The emergence of several SARS-CoV-2 variants of concern (VOC) with multiple amino acid replacements has implications for the future control of the COVID-19 pandemic (Davies et al., 2020; Kirby, 2021; Tegally et al., 2020; Volz et al., 2021). Variants of concern include the UK (United Kingdom) variant 501Y.V1 lineage B.1.1.7 (Davies et al., 2020), the SA (South Africa) variant 501Y.V2 lineage B.1.351 (Tegally et al., 2020), the BR (Brazilian) variant 501Y.V3 lineage P.1 (Voloch et al., 2020), and the CA (California) variant CAL.20C lineage B.1.427 (Zhang et al., 2021). The B.1.1.7 variant is associated with increased transmissibility (Rambaut et al., 2020;Washington et al., 2021), and similar epidemiological observations have been reported for the SA and BR variants (Tegally et al., 2020; Voloch et al., 2020).
Mutations of greatest concern are present in the viral Spike (S) protein, and include notable mutations in the receptor binding domain (RBD), N-terminal domain (NTD), and furin cleavage site region. Several of these mutations directly affect ACE2 receptor binding affinity, which may impact infectivity, viral load, or transmissibility (Greaney et al., 2021; Starr et al., 2021; Wang et al., 2021a; Zahradník et al., 2021).
Several of these mutations were also noted to be in regions bound by neutralizing antibodies, so it is crucial to address to what extent the mutations associated with the variants impact immunity induced by either SARS-CoV-2 infection or vaccination.
Several reports address the effect of these mutations on antibody binding and function, by either monoclonal or polyclonal antibody responses, and considering both natural infection or vaccination (Edara et al., 2021; Greaney et al., 2021; Muik et al., 2021; Shen et al., 2021; Skelly et al., 2020; Stamatatos et al., 2021; Supasa et al., 2021; Wang et al., 2021a; Wang et al., 2021b; Wibmer et al., 2021; Wu et al., 2021).
In general, the impact of the B.1.1.7 variant mutations on neutralizing antibody titers is moderate (Emary et al., 2021; Muik et al., 2021; Shen et al., 2021; Skelly et al., 2020; Supasa et al., 2021; Wu et al., 2021).
In contrast, the mutations associated with the B.1.351 and P.1.variants are associated with more pronounced loss of neutralizing capacity (Cele et al., 2021; Skelly et al., 2020; Wang et al., 2021a; Wibmer et al., 2021; Wu et al., 2021). Concerning vaccination responses, the
AstraZeneca ChAdOx1 vaccine has been associated with a partial loss of neutralizing antibody activity against B.1.1.7 (Skelly et al., 2020),
and a large loss of neutralizing activity against B.1.351 (Voysey et al., 2021).
Consistent with these reports, ChAdOx1 maintains efficacy against B.1.1.7 (Emary et al., 2021; Hall et al., 2021),
but has a major loss in efficacy against mild COVID-19 with the B.1.351 variant (Voysey et al., 2021).
Current epidemiological evidence is that the BNT162b2 Pfizer/ BioNTechCOVID-19 vaccine retains its efficacy against B.1.1.7 in the UK and in reports from Israel (Amit et al., 2021).
Novavax (NVX-CoV2373) has reported differential protective immunity against the parental strain, B.1.1.7, and B.1.351in vaccine clinical trials (96%, 86%, and 60%) (Novavax Inc., 2021),
whereas the Janssen Ad26.COV2.S1-dose COVID-19 vaccine, which elicits lower neutralizing antibody titers (Sadoff et al., 2021),
has relatively similar protection for moderate COVID-19 against both the ancestral strain and B.1.351 (72% and 64%) (FDA, 2021a, b).
Several lines of evidence suggest that CD4+ and CD8+ T cell responses play important roles in resolution of SARS-CoV-2 infection and COVID-19 (Sette and Crotty, 2021),
including modulating disease severity in humans (Rydyznski Moderbacher et al., 2020; Tan et al., 2021)
and reducing viral loads in non-human primates (Munoz-Fontela et al., 2020).
Further, persons with agammaglobulinemia or pharmaceutical depletion of B cells generally experience an uncomplicated COVID-19 disease course (Sette and Crotty, 2021; Soresina et al., 2020).
Robust CD4+ and CD8+ T cell memory is induced after COVID-19 (Breton et al., 2021; Dan et al., 2021; Peng et al., 2020; Wang et al., 2021b),
and multiple COVID-19 vaccines elicit CD4+ and CD8+ T cell responses (Baden et al., 2021; Dowd et al., 2020; Keech et al., 2020; Sadoff et al., 2021; Voysey et al., 2021).
It is therefore key to address the potential impact of SARS-CoV-2 variants mutations on T cell reactivity; however, little data is currently available on this topic (Skelly et al., 2020).
Here, we take a combined experimental and bioinformatics approach to address how SARS-CoV-2 variants of concern impact T cell reactivity. We directly assess T cell responses from persons recovered from COVID-19 obtained before the emergence of the variants, and from persons who were recently vaccinated with either the Moderna mRNA-1273 or Pfizer/BioNTechBNT162b2 vaccines, for their capacity to recognize peptides derived from the ancestral reference sequence and the B.1.1.7, B1.351, P.1and the CAL.20C variants. Bioinformatic analyses were used to predict the impact of mutations in the various variants with sets of previously reported CD4+ and CD8+ T cell epitopes derived from the ancestral reference sequence (Tarke et al., 2021).
