Vaccines against the original strain of SARS-CoV-2 provide T cell memory to the B.1.1.529 variant

Abstract

Background The SARS-CoV-2 variant B.1.1.529 potentially escapes immunity from vaccination via a heavily mutated Spike protein. Here, we analyzed whether T cell memory towards the B.1.1.529 Spike protein is present in individuals who received two or three doses of vaccines designed against the original Wuhan strain of SARS-CoV-2. Methods PBMCs were isolated from two- and three-times vaccinated study participants and incubated in vitro with peptide pools of the Spike protein derived from sequences of the original Wuhan or the B.1.1.529 strains of SARS-CoV-2. Activated antigen-specific T cells were detected by flow cytometry. In silico analyses with NetMHCpan and NetMHCIIpan were used to determine differences in MHC class presentation between the original strain and the B.1.1.529 strain for the most common MHCs in the European-Caucasian population. Results Here we show, that both CD4 and CD8 responses to the B.1.1.529 Spike protein are marginally reduced compared to the ancestor protein and a robust T cell response is maintained. Epitope analyses reveal minor differences between the two SARS-CoV-2 strains in terms of MHC class presentations for the MHC-alleles being most common in the European-Caucasian population. Conclusions The memory T cell response induced via first generation vaccination remains robust and is mostly unaffected by B.1.1.529 mutations. Correspondingly, in silico analyses of MHC presentation of epitopes derived from the B.1.1.529 Spike protein shows marginal differences compared to the ancestral SARS-CoV-2 strain.

A Multi-Epitope/CXCL11 Prime/Pull Coronavirus Mucosal Vaccine Boosts the Frequency and the Function of Lung-Resident CD4+and CD8+Memory T Cells and Protects Against COVID-19-like Symptoms and Death Caused by SARS-CoV-2 infection

“…In addition, unlike antibody-based vaccines, T-cell-based vaccines have the potential to protect against new and mutated strains of the virus (27).…”

Cross-Reactivity Assessment of Vaccine-Derived SARS-CoV-2 T Cell Responses against BA.2.86 and JN.1

“…Our assessment of SARS-CoV-2 T cell cross-reactivity against BA.2.86 and JN.1 is based on epitope conservation analysis. This method has proven to be reliable for assessing the cross-reactivity of T cell responses to SARS-CoV-2 as well as other viruses including SARS-CoV-1, dengue virus, and monkeypox virus [38,[42][43][44], and the predictions have aligned closely with experimental studies [18][19][20][21][22]45]. Nonetheless, the experimental quan-tification of T cell cross-reactivity against BA.2.86 and JN.1 is still required.…”

“…To assess whether an identified epitope mutant affects binding between the associated epitope and its corresponding HLA allele, we employed established peptide-HLA binding prediction tools, netMHCIIpan4.0 [16] (for CD4+ T cell epitopes) and netMHCpan4.1 [17] (for CD8+ T cell epitopes). The predictions of these computational tools have lined up well with SARS-CoV-2 experimental studies describing T cell epitopes [18][19][20], as well as those reporting the HLA binding of specific T cell epitopes [21,22]. For all predictions, we utilized the eluted ligand percentile ranks generated by both methods that take into account peptide-MHC binding affinity as well as antigen processing and presentation.…”

Immunogenicity and efficacy of a novel multi-patch SARS-CoV-2/COVID-19 vaccine candidate

“…The clinical studies have provided solid evidence that the administration of these vaccines in humans efficiently protects against severe disease, hospitalizations and death across age groups and in diverse populations ( 75 – 81 ). However, this protection was maintained for a limited time, generally about 6 months, and was affected by the emergence of SARS-CoV-2 VoCs, being the neutralization response more prone to decay compared with the cellular immunity ( 13 , 82 ). For this reason, the regulatory authorities (FDA and EMA) and WHO have recommended the administration of booster doses in order to prolong the duration of immune responses and to increase the protection capacity against highly mutated VoCs.…”