Mandatory preventive vaccines for infectious diseases expressing T-cell epitopes for cancer prevention.

IF 3.1 2区 医学 Q3 IMMUNOLOGY
Concetta Ragone, Angela Mauriello, Beatrice Cavalluzzo, Simona Mangano, Biancamaria Cembrola, Noemi Ciotola, Luigi Buonaguro, Maria Tagliamonte
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引用次数: 0

Abstract

We have previously reported that microorganism-associated antigens (MAAs) share high sequence and conformational homology with tumor-associated antigens (TAAs) as well as T cells cross-react with homologous MAA/TAA pairs. More recently, we have also shown that the SARS-CoV-2 preventive vaccine, besides the humoral response, is able to elicit also a T cell response which cross-react with homologous TAAs. In the present study we analyzed the mandatory pediatric vaccines, namely the hexavalent vaccine (Diphtheria, Tetanus, Pertussis (whooping cough), Polio, Haemophilus influenzae type b (Hib), Hepatitis B) and the MMR (measles, mumps and rubella), and the chickenpox vaccine. MHC class I epitopes (9 mers) from each of these vaccines were predicted for the most frequent 12 HLA A and B alleles. Overall, 3177 strong binders (SBs) were identified and the most frequently associated allele is the HLA-A*02:01. Of these, 397 are predicted for the hexavalent vaccine and 571 in the MMR vaccine. A molecular mimicry with 59 SBs derived from cellular proteins has been identified and 13 of these proteins are significantly overexpressed in several human cancers. All these results strongly suggest that the mandatory pediatric vaccinations may potentially elicit a CD8+ T cell response against several microbial epitopes in individuals with different genetic background. Such microbial epitopes show high homology with epitopes from cellular proteins overexpressed in multiple cancer types. Therefore, a potential anti-microbial CD8+ T cell response may cross-react against cancer cells. This would imply that the pediatric vaccinations may be a preventive measure against both microbial infections and a broad spectrum of tumors. A large-scale immune-epidemiological study will be needed to confirm the proposed suggestive results.

表达t细胞表位的传染性疾病强制性预防疫苗用于癌症预防。
我们以前报道过微生物相关抗原(MAAs)与肿瘤相关抗原(TAAs)具有高序列和构象同源性,并且T细胞与同源MAA/TAA对交叉反应。最近,我们还表明,SARS-CoV-2预防性疫苗,除了体液反应外,还能够引发与同源TAAs交叉反应的T细胞反应。在本研究中,我们分析了强制性儿童疫苗,即六价疫苗(白喉、破伤风、百日咳、脊髓灰质炎、b型流感嗜血杆菌(Hib)、乙型肝炎)和MMR(麻疹、腮腺炎和风疹),以及水痘疫苗。预测每种疫苗中最常见的12个HLA A和B等位基因的MHC I类表位(9 mers)。总共鉴定出3177个强结合体(SBs),最常见的相关等位基因是HLA-A*02:01。其中,六价疫苗预计有397种,MMR疫苗预计有571种。已经鉴定出一种源自细胞蛋白的具有59种SBs的分子模拟,其中13种蛋白质在几种人类癌症中显着过表达。所有这些结果强烈表明,强制性儿童疫苗接种可能潜在地引发CD8+ T细胞对具有不同遗传背景的个体的几种微生物表位的反应。这些微生物表位与多种癌症类型中过度表达的细胞蛋白表位具有高度的同源性。因此,潜在的抗微生物CD8+ T细胞反应可能与癌细胞交叉反应。这意味着儿童疫苗接种可能是一种预防微生物感染和广谱肿瘤的措施。需要进行大规模的免疫流行病学研究来证实提出的具有启发性的结果。
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来源期刊
Infectious Agents and Cancer
Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY
CiteScore
5.80
自引率
2.70%
发文量
54
期刊介绍: Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.
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