The adaptive immune response to severe acute respiratory coronavirus 2 (SARS-CoV-2) is important for vaccine development and in the recovery from coronavirus disease 2019 (COVID-19). Men and cancer patients have been reported to be at higher risks of contracting the virus and developing the more severe forms of COVID-19. Prostate cancer (PCa) may be associated with both of these risks. We show that CD4+ T cells of SARS-CoV-2-unexposed patients with hormone-refractory (HR) metastatic PCa had decreased CD4+ T cell immune responses to antigens from SARS-CoV-2 spike glycoprotein but not from the spiked glycoprotein of the 'common cold'-associated human coronavirus 229E (HCoV-229E) as compared with healthy male volunteers who responded comparably to both HCoV-229E- and SARS-CoV-2-derived antigens. Moreover, the HCoV-229E spike glycoprotein antigen-elicited CD4+ T cell immune responses cross-reacted with the SARS-CoV-2 spiked glycoprotein antigens. PCa patients may have impaired responses to the vaccination, and the cross-reactivity can mediate antibody-dependent enhancement (ADE) of COVID-19. These findings highlight the potential for increased vulnerability of PCa patients to COVID-19.

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czechia

Department of Technical Operations SOTIO a s Prague Czechia

Zobrazit více v PubMed

Dyer O. Covid-19: Black People and Other Minorities are Hardest Hit in US. BMJ (2020) 369:m1483.  10.1136/bmj.m1483 PubMed DOI

Chen J, Qi T, Liu L, Ling Y, Qian Z, Li T, et al. . Clinical Progression of Patients With COVID-19 in Shanghai, China. J Infect (2020) 80(5):e1–6.  10.1016/j.jinf.2020.03.004 PubMed DOI PMC

Zhang L, Zhu F, Xie L, Wang C, Wang J, Chen R, et al. . Clinical Characteristics of COVID-19-infected Cancer Patients: A Retrospective Case Study in Three Hospitals Within Wuhan, China. Ann Oncol: Off J Eur Soc Med Oncol ESMO (2020).  10.1016/j.annonc.2020.03.296 PubMed DOI PMC

Mehta V, Goel S, Kabarriti R, Cole D, Goldfinger M, Acuna-Villaorduna A, et al. . Case Fatality Rate of Cancer Patients With COVID-19 in a New York Hospital System. Cancer Discovery (2020).  10.1158/2159-8290.CD-20-0516 PubMed DOI PMC

Jin JM, Bai P, He W, Wu F, Liu XF, Han DM, et al. . Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health (2020) 8:152.  10.3389/fpubh.2020.00152 PubMed DOI PMC

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2019. CA: Cancer J Clin (2019) 69(1):7–34.  10.3322/caac.21551 PubMed DOI

Sama IE, Ravera A, Santema BT, van Goor H, Ter Maaten JM, Cleland JGF, et al. . Circulating Plasma Concentrations of Angiotensin-Converting Enzyme 2 in Men and Women With Heart Failure and Effects of Renin-Angiotensin-Aldosterone Inhibitors. Eur Heart J (2020) 41(19):1810–7.  10.1093/eurheartj/ehaa373 PubMed DOI PMC

Paces J, Strizova Z, Smrz D, Cerny J. Covid-19 and the Immune System. Physiol Res (2020).  10.33549/physiolres.934492 PubMed DOI PMC

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. . Clinical Features of Patients Infected With 2019 Novel Coronavirus in Wuhan, China. Lancet (2020) 395(10223):497–506.  10.1016/S0140-6736(20)30183-5 PubMed DOI PMC

Braciale TJ, Hahn YS. Immunity to Viruses. Immunol Rev (2013) 255(1):5–12.  10.1111/imr.12109 PubMed DOI PMC

Kang SM, Compans RW. Host Responses From Innate to Adaptive Immunity After Vaccination: Molecular and Cellular Events. Mol Cells (2009) 27(1):5–14.  10.1007/s10059-009-0015-1 PubMed DOI PMC

Grifoni A, Weiskopf K, Ramirez SI, Mateus J, Dan J M, Moderbacher C R, et al. . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans With COVID-19 Disease and Unexposed Individuals. Cell (Forthcoming 2020).  10.1016/j.cell.2020.05.015. PubMed DOI PMC

Subramaniam KS, Lant S, Goodwin L, Grifoni A, Weiskopf D, Turtle L. Two Is Better Than One: Evidence for T-Cell Cross-Protection Between Dengue and Zika and Implications on Vaccine Design. Front Immunol (2020) 11:517.  10.3389/fimmu.2020.00517 PubMed DOI PMC

Balz K, Trassl L, Hartel V, Nelson PP, Skevaki C. Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development. Front Immunol (2020) 11:513.  10.3389/fimmu.2020.00513 PubMed DOI PMC

Hotez PJ, Corry DB, Bottazzi ME. Covid-19 Vaccine Design: The Janus Face of Immune Enhancement. Nat Rev Immunol (2020).  10.1038/s41577-020-0323-4 PubMed DOI PMC

Ricke D. Ricke, Darrell and Malone, Robert W., Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (Ade) (2/27/2020). (2020). Available at: https://ssrn.com/abstract=3546070 10.2139/ssrn.3546070. DOI

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. . Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and its Immune Cross-Reactivity With SARS-Cov. Nat Commun (2020) 11(1):1620.  10.1038/s41467-020-15562-9 PubMed DOI PMC

Li Z, Tomlinson AC, Wong AH, Zhou D, Desforges M, Talbot PJ, et al. . The Human Coronavirus HCoV-229E s-Protein Structure and Receptor Binding. eLife (2019) 8.  10.7554/eLife.51230 PubMed DOI PMC

Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Sochorova K, et al. . Phase I/II Clinical Trial of Dendritic-Cell Based Immunotherapy (DCVAC/Pca) Combined With Chemotherapy in Patients With Metastatic, Castration-Resistant Prostate Cancer. Oncotarget (2015) 6(20):18192–205.  10.18632/oncotarget.4145 PubMed DOI PMC

Taborska P, Bartunkova J, Smrz D. Simultaneous In Vitro Generation of Human CD34(+)-derived Dendritic Cells and Mast Cells From non-Mobilized Peripheral Blood Mononuclear Cells. J Immunol Methods (2018) 458:63–73.  10.1016/j.jim.2018.04.005 PubMed DOI

Taborska P, Stakheev D, Strizova Z, Vavrova K, Podrazil M, Bartunkova J, et al. . Personalized Ex Vivo Multiple Peptide Enrichment and Detection of T Cells Reactive to Multiple Tumor-Associated Antigens in Prostate Cancer Patients. Med Oncol (2017) 34(10):173.  10.1007/s12032-017-1035-x PubMed DOI

Currier JR, Kuta EG, Turk E, Earhart LB, Loomis-Price L, Janetzki S, et al. . A Panel of MHC Class I Restricted Viral Peptides for Use as a Quality Control for Vaccine Trial ELISPOT Assays. J Immunol Methods (2002) 260(1-2):157–72.  10.1016/s0022-1759(01)00535-x PubMed DOI

Stakheev D, Taborska P, Strizova Z, Podrazil M, Bartunkova J, Smrz D. The WNT/beta-catenin Signaling Inhibitor XAV939 Enhances the Elimination of LNCaP and PC-3 Prostate Cancer Cells by Prostate Cancer Patient Lymphocytes In Vitro. Sci Rep (2019) 9(1):4761.  10.1038/s41598-019-41182-5 PubMed DOI PMC

Wu SQ, Su H, Wang YH, Zhao XK. Role of Tumor-Associated Immune Cells in Prostate Cancer: Angel or Devil? Asian J Andrology (2019) 21(5):433–7.  10.4103/aja.aja_47_19 PubMed DOI PMC

Zou L, Dai L, Zhang Y, Fu W, Gao Y, Zhang Z, et al. . Clinical Characteristics and Risk Factors for Disease Severity and Death in Patients With Coronavirus Disease 2019 in Wuhan, China. Front Med (2020) 7:532.  10.3389/fmed.2020.00532 PubMed DOI PMC

Cohen JF, Korevaar DA, Matczak S, Chalumeau M, Allali S, Toubiana J. Covid-19-Related Fatalities and Intensive-Care-Unit Admissions by Age Groups in Europe: A Meta-Analysis. Front Med (2020) 7:560685.  10.3389/fmed.2020.560685 PubMed DOI PMC

Saletti G, Gerlach T, Jansen JM, Molle A, Elbahesh H, Ludlow M, et al. . Older Adults Lack SARS CoV-2 Cross-Reactive T Lymphocytes Directed to Human Coronaviruses OC43 and NL63. Sci Rep (2020) 10(1):21447.  10.1038/s41598-020-78506-9 PubMed DOI PMC

Amanat F, Krammer F. SARS-Cov-2 Vaccines: Status Report. Immunity (2020) 52(4):583–9.  10.1016/j.immuni.2020.03.007 PubMed DOI PMC

Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell (2020) 181(2):281–92.e286.  10.1016/j.cell.2020.02.058 PubMed DOI PMC

DiPiazza A, Richards KA, Knowlden ZA, Nayak JL, Sant AJ. The Role of CD4 T Cell Memory in Generating Protective Immunity to Novel and Potentially Pandemic Strains of Influenza. Front Immunol (2016) 7:10.  10.10.3389/fimmu.2016.00010 PubMed DOI PMC

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. . Dysregulation of Immune Response in Patients With COVID-19 in Wuhan, China. Clin Infect Dis: an Off Publ Infect Dis Soc America (2020).  10.1093/cid/ciaa248 PubMed DOI PMC

Giwa AL, Desai A, Duca A. Novel 2019 Coronavirus SARS-CoV-2 (Covid-19): An Overview for Emergency Clinicians. Pediatr Emergency Med Pract (2020) 17(5):1–24. PubMed

Cai C, Ahmed OA, Shen H, Zeng S. Which Cancer Type has the Highest Risk of COVID-19 Infection? J Infect (2020).  10.1016/j.jinf.2020.05.028 PubMed DOI PMC

Reber AJ, Music N, Kim JH, Gansebom S, Chen J, York I. Extensive T Cell Cross-Reactivity Between Diverse Seasonal Influenza Strains in the Ferret Model. Sci Rep (2018) 8(1):6112.  10.1038/s41598-018-24394-z PubMed DOI PMC

Iwasaki A, Yang Y. The Potential Danger of Suboptimal Antibody Responses in COVID-19. Nat Rev Immunol (2020).  10.1038/s41577-020-0321-6 PubMed DOI PMC

Tetro JA. Is COVID-19 Receiving ADE From Other Coronaviruses? Microbes Infect Institut Pasteur (2020) 22(2):72–3.  10.1016/j.micinf.2020.02.006 PubMed DOI PMC

Bajaj V, Gadi N, Spihlman AP, Wu SC, Choi CH, Moulton VR. Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections? Front Physiol (2020) 11:571416.  10.3389/fphys.2020.571416 PubMed DOI PMC

Chen Y, Klein SL, Garibaldi BT, Li H, Wu C, Osevala NM, et al. . Aging in COVID-19: Vulnerability, Immunity and Intervention. Ageing Res Rev (2021) 65:101205.  10.1016/j.arr.2020.101205 PubMed DOI PMC

Cao X. Covid-19: Immunopathology and its Implications for Therapy. Nat Rev Immunol (2020) 20(5):269–70.  10.1038/s41577-020-0308-3 PubMed DOI PMC

Effectiveness and Durability of mRNA Vaccine-Induced SARS-CoV-2-Specific Humoral and Cellular Immunity in Severe Asthma Patients on Biological Therapy

SARS-CoV-2 spike glycoprotein-reactive T cells can be readily expanded from COVID-19 vaccinated donors