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

Abstract

Highlights d T cells of exposed donors or vaccinees effectively recognize SARS-CoV-2 variants d Effective recognition in AIM and FluoroSPOT assays, for spike and other proteins d 93% and 97% of CD4 and CD8 epitopes are 100% conserved across variants

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

“…It is also reassuring to find that the majority of T cell responses in recipients of two doses of the BNT162b2 vaccine are generated by epitopes that are invariant between the prototype and two of the current VOC (B.1.1.7 and B.1.351). These data are compatible with a recent report that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the B.1.1.7 or B.1.351 variants 49 , with no significant differences observed in CD4 and CD8 responses to a pool of S peptides corresponding to the ancestral sequence and those corresponding to the different variants. T cell responses to SARS-CoV-2 are known to target a wide range of regions in spike 50 .…”

Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history

“…The B.1.1.7 variant was detected in 85% of the breakthrough infections. While antibody neutralization of emerging variants may be reduced in comparison with the ancestral strain of SARS-CoV-2, T cell reactivity following vaccination or natural infection has been shown to be similar across strains and may reduce the severity of COVID-19 if a breakthrough infection occurs 8 . The decline in antibody levels over three months post-vaccination, and the relatively reduced neutralization of variants of concern, point to an urgent need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.…”

A ‘mix and match’ approach to SARS-CoV-2 vaccination

“…Neutralizing spike protein-specific antibodies are capable of preventing infection with SARS-CoV-2 in animal models, and these antibodies have served as the marker for a protective vaccine response, although precise thresholds have not been confirmed in humans 7 . Although seroconversion is more readily assessed, T cell responses also contribute to viral clearance after infection; these may generate a more-robust response to recently emergent variants, and may be generated even in the absence of detectable antibody responses in immunocompromised transplant recipients 8,9 . Incorporating vaccines that elicit mainly humoral responses (e.g., protein-based vaccines) and those that elicit strong cellular responses (e.g., viral vectorbased vaccines) into heterologous primeboost platforms may therefore improve the breadth of immunity to SARS-CoV-2 10 .…”