在本研究中，我们研究了来自整个 SARS-CoV-2 蛋白质组的肽是否与 TAA（肿瘤相关抗原）具有同源性，并且 BNT162b2 预防性疫苗或 SARS-CoV-2 是否可以引发交叉反应性 CD8 T 细胞自然感染。预测与 HLA-A*02:01 等位基因具有高亲和力 (<100nM) 的病毒表位。鉴定了共享的和变体特异性的表位。 SARS-CoV-2 肽和多种 TAA 之间发现氨基酸序列显着同源，主要与乳腺癌、肝癌、黑色素瘤和结肠癌相关。在所有病毒蛋白中都发现了病毒表位和 TAA 的分子模拟，主要是 Orf 1ab 和 Spike（BNT162b2 疫苗中包含的蛋白）。预测的结构相似性证实了序列同源性，并且观察到了与 HLA 和 TCR α 链和 β 链的可比接触模式。通过MHC l-右旋体染色发现了与配对肽发生交叉反应的CD8 T细胞克隆。我们的结果首次表明，几种SARS-COV-2抗原与TAA高度同源，并鉴定出交叉反应T细胞在感染者和 BNT162b2 预防性疫苗接种者中。这意味着 SARS-Cov-2 大流行可能代表乳腺癌、肝癌、黑色素瘤和结肠癌的自然预防性免疫。未来几年，现实世界的证据将为此类免疫学实验证据提供最终证明。此外，此类SARS-CoV-2表位可用于开发“多癌症”现成的预防/治疗性疫苗制剂，其比过度表达的肿瘤自身抗原具有更高的抗原性和免疫原性，具有潜在的宝贵益处全世界数以千计的癌症患者。版权所有 © 2024 Ragone、Mauriello、Cavaluzzo、Cavalcanti、Russo、Manolio、Mangano、Cembrola、Tagliamonte 和 Buonaguro。

In the present study we investigated whether peptides derived from the entire SARS-CoV-2 proteome share homology to TAAs (tumor-associated antigens) and cross-reactive CD8+ T cell can be elicited by the BNT162b2 preventive vaccine or the SARS-CoV-2 natural infection.Viral epitopes with high affinity (<100nM) to the HLA-A*02:01 allele were predicted. Shared and variant-specific epitopes were identified. Significant homologies in amino acidic sequence have been found between SARS-CoV-2 peptides and multiple TAAs, mainly associated with breast, liver, melanoma and colon cancers. The molecular mimicry of the viral epitopes and the TAAs was found in all viral proteins, mostly the Orf 1ab and the Spike, which is included in the BNT162b2 vaccine. Predicted structural similarities confirmed the sequence homology and comparable patterns of contact with both HLA and TCR α and β chains were observed. CD8+ T cell clones cross-reactive with the paired peptides have been found by MHC class l-dextramer staining.Our results show for the first time that several SARS-COV-2 antigens are highly homologous to TAAs and cross-reactive T cells are identified in infected and BNT162b2 preventive vaccinated individuals. The implication would be that the SARS-Cov-2 pandemic could represent a natural preventive immunization for breast, liver, melanoma and colon cancers. In the coming years, real-world evidences will provide the final proof for such immunological experimental evidence. Moreover, such SARS-CoV-2 epitopes can be used to develop "multi-cancer" off-the-shelf preventive/therapeutic vaccine formulations, with higher antigenicity and immunogenicity than over-expressed tumor self-antigens, for the potential valuable benefit of thousands of cancer patients around the World.Copyright © 2024 Ragone, Mauriello, Cavalluzzo, Cavalcanti, Russo, Manolio, Mangano, Cembrola, Tagliamonte and Buonaguro.