Spike-directed vaccination elicits robust spike-specific T-cell response, including to mutant strains

Abstract

Although most studies describing coronavirus disease 2019 vaccine responses have focused on antibodies, there is increasing evidence that T cells play a critical role. Here the authors evaluated T-cell responses in seronegative donors before and after vaccination to define responses to the severe acute respiratory syndrome coronavirus 2 reference strain as well as to mutations in the variant strains Alpha/B.1.1.7 and Beta/B.1.351. The authors observed enhanced T-cell responses to reference and variant spike strains post-vaccination.

Cellular therapies for the treatment and prevention of SARS-CoV-2 infection

“…[83][84][85] Importantly, high throughput systematic analysis of CD8 + T cell activity in response to mutant peptides from SARS-CoV-2 variants of concern-including alpha, beta, and delta variants-has suggested decreased ability of some mutant epitopes to bind to certain HLA, 86,87 which highlights the need to ensure that CSTs generated for clinical use maintain activity against circulating strains as new variants arise. 72 SARS-CoV-2-specific T cells are longlasting in convalescent individuals, retaining activation and proliferation capacity ex vivo for at least 10 months, 88 and supporting the assertion that CSTs may provide durable protection against severe illness due to SARS-CoV-2, even as humoral immunity wanes. 89…”

“…[67][68][69][70][71] Moreover, these spikedirected T cell responses elicited from vaccinated but previously uninfected donors against peptide pools created from the Wuhan strain, have shown cross reactivity to other variant strains thereby broadening the applicability of this approach. 72 Currently, there are seven registered phase I/II trials evaluating allogeneic CSTs for the treatment or prevention of COVID-19, four of which are actively recruiting patients (Table 1).…”

“…Studies to date demonstrate moderate to high T cell cross-reactivity against circulating variants, including the Omicron variant, [74][75][76] with strong reactivity particularly in the CD4 + compartment. 67,70,72,[77][78][79] Indeed, T cell epitopes identified in CSTs from convalescent patients span the viral proteome 40,50,[80][81][82] and stimulate T cell responses to viral variants that are partially resistant to vaccine-induced humoral spikespecific responses. [83][84][85] Importantly, high throughput systematic analysis of CD8 + T cell activity in response to mutant peptides from SARS-CoV-2 variants of concern-including alpha, beta, and delta variants-has suggested decreased ability of some mutant epitopes to bind to certain HLA, 86,87 which highlights the need to ensure that CSTs generated for clinical use maintain activity against circulating strains as new variants arise.…”

Coronavirus disease 2019 (COVID-19) vaccine platforms: how novel platforms can prepare us for future pandemics: a narrative review

“…With the recent emergence of the omicron variant, two doses of Comirnaty were reported by Pfizer to confer protection against any severe disease, although a booster dose is recommended. Since the majority of the epitopes on the S protein of the omicron variant are predicted to maintain their ability for human leukocyte antigen-epitope binding, vaccines such as Comirnaty that focus on the S protein are expected to elicit a sufficiently robust T cell immunity against VOCs such as omicron [34][35][36]. A study on the effectiveness of Pfizer's Comirnaty and Astra-Zeneca's ChAdOX1 against the delta (B.1.617.2) variant demonstrated that the efficacy of both vaccines was lower for the delta variant than for the alpha (B.1.1.7) variant [37].…”

Antigen-Specific T Cells and SARS-CoV-2 Infection: Current Approaches and Future Possibilities

“…CST products can be generated not only from virus-experienced but also virus-naive donors, as SARS-CoV-2-specific T cell responses were observed in some unexposed individuals, likely due to pre-existing cross-reactivity with common seasonal coronaviruses [ 73 , 146 , 163 , 164 , 165 ]. The pool of potential donors can be also enriched with individuals vaccinated against SARS-CoV-2 [ 166 , 167 , 168 ], whose specific T cell responses have been proven effective against other virus variants [ 169 , 170 ]. The generation of CSTs from vaccinated donors on a clinically relevant scale was successfully demonstrated for the first time by Taborska et al [ 171 ].…”