Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

Michael Har-Noy, Reuven Or, Michael Har-Noy, Reuven Or

Abstract

Background: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X'. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim®) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter.

Conclusion: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.

Keywords: COVID-19; Cell therapy; Immunosenescence; Immunotherapy; Inflammaging; Vaccine.

Conflict of interest statement

MHN is the Founder of Immunovative Therapies, Ltd. and Mirror Biologics, Inc which own patent rights to AlloStim®.

References

    1. Operschall E, Pavlovic J, Nawrath M, Molling K. Mechanism of protection against influenza A virus by DNA vaccine encoding the hemagglutinin gene. Intervirology. 2000;43:322–330. doi: 10.1159/000054000.
    1. Carrat F, Flahault A. Influenza vaccine: the challenge of antigenic drift. Vaccine. 2007;25:6852–6862. doi: 10.1016/j.vaccine.2007.07.027.
    1. Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc Natl Acad Sci USA. 2020;117:9241–9243. doi: 10.1073/pnas.2004999117.
    1. Oxenius A, Price DA, Hersberger M, Schlaepfer E, Weber R, Weber M, Kundig TM, Boni J, Joller H, Phillips RE, et al. HIV-specific cellular immune response is inversely correlated with disease progression as defined by decline of CD4+ T cells in relation to HIV RNA load. J Infect Dis. 2004;189:1199–1208. doi: 10.1086/382028.
    1. Nakamura I, Imawari M. Cellular immune response in HCV infection. J Gastroenterol. 2000;35:881–889. doi: 10.1007/s005350070001.
    1. Kash JC, Muhlberger E, Carter V, Grosch M, Perwitasari O, Proll SC, Thomas MJ, Weber F, Klenk HD, Katze MG. Global suppression of the host antiviral response by Ebola- and Marburgviruses: increased antagonism of the type I interferon response is associated with enhanced virulence. J Virol. 2006;80:3009–3020. doi: 10.1128/JVI.80.6.3009-3020.2006.
    1. Cassaniti I, Percivalle E, Adzasehoun KMG, Comolli G, Baldanti F. Dengue virus-specific humoral and T cellular immune response in italian residents and travelers returning from endemic areas. Vector Borne Zoonotic Dis. 2020;20:295–302. doi: 10.1089/vbz.2019.2515.
    1. Chen J, Lau YF, Lamirande EW, Paddock CD, Bartlett JH, Zaki SR, Subbarao K. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. J Virol. 2010;84:1289–1301. doi: 10.1128/JVI.01281-09.
    1. Chen D, Xu W, Lei Z, Huang Z, Liu J, Gao Z, Peng L. Recurrence of positive SARS-CoV-2 RNA in COVID-19: a case report. Int J Infect Dis. 2020;93:297–299. doi: 10.1016/j.ijid.2020.03.003.
    1. Panagioti E, Klenerman P, Lee LN, van der Burg SH, Arens R. Features of effective T cell-inducing vaccines against chronic viral infections. Front Immunol. 2018;9:276. doi: 10.3389/fimmu.2018.00276.
    1. Clemens EB, van de Sandt C, Wong SS, Wakim LM, Valkenburg SA. Harnessing the power of T cells: the promising hope for a universal influenza vaccine. Vaccines. 2018;6(2):18. doi: 10.3390/vaccines6020018.
    1. Kirkwood KL. Inflammaging. Immunol Invest. 2018;47:770–773. doi: 10.1080/08820139.2018.1552392.
    1. Ventura MT, Casciaro M, Gangemi S, Buquicchio R. Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clin Mol Allergy. 2017;15:21. doi: 10.1186/s12948-017-0077-0.
    1. Dosch SF, Mahajan SD, Collins AR. SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-kappaB pathway in human monocyte macrophages in vitro. Virus Res. 2009;142:19–27. doi: 10.1016/j.virusres.2009.01.005.
    1. Horvath CM, Darnell JE., Jr The antiviral state induced by alpha interferon and gamma interferon requires transcriptionally active Stat1 protein. J Virol. 1996;70:647–650. doi: 10.1128/JVI.70.1.647-650.1996.
    1. Yan N, Chen ZJ. Intrinsic antiviral immunity. Nat Immunol. 2012;13:214–222. doi: 10.1038/ni.2229.
    1. Cornberg M, Clute SC, Watkin LB, Saccoccio FM, Kim SK, Naumov YN, Brehm MA, Aslan N, Welsh RM, Selin LK. CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections. J Immunol. 2010;184:2825–2838. doi: 10.4049/jimmunol.0902168.
    1. Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr Opin Immunol. 2001;13:114–119. doi: 10.1016/S0952-7915(00)00191-6.
    1. Breloer M, Dorner B, More SH, Roderian T, Fleischer B, von Bonin A. Heat shock proteins as “danger signals”: eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-gamma production in T cells. Eur J Immunol. 2001;31:2051–2059. doi: 10.1002/1521-4141(200107)31:7<2051::AID-IMMU2051>;2-H.
    1. Wati S, Soo ML, Zilm P, Li P, Paton AW, Burrell CJ, Beard M, Carr JM. Dengue virus infection induces upregulation of GRP78, which acts to chaperone viral antigen production. J Virol. 2009;83:12871–12880. doi: 10.1128/JVI.01419-09.
    1. Menoret A. Purification of recombinant and endogenous HSP70s. Methods. 2004;32:7–12. doi: 10.1016/S1046-2023(03)00180-4.
    1. Zhang X, Mosser DM. Macrophage activation by endogenous danger signals. J Pathol. 2008;214:161–178. doi: 10.1002/path.2284.
    1. Fournier P, Arnold A, Schirrmacher V. Polarization of human monocyte-derived dendritic cells to DC1 by in vitro stimulation with newcastle disease virus. J BUON. 2009;14(Suppl 1):S111–S122.
    1. Berberich C, Ramirez-Pineda JR, Hambrecht C, Alber G, Skeiky YA, Moll H. Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens. J Immunol. 2003;170:3171–3179. doi: 10.4049/jimmunol.170.6.3171.
    1. Ahuja SS, Mummidi S, Malech HL, Ahuja SK. Human dendritic cell (DC)-based anti-infective therapy: engineering DCs to secrete functional IFN-gamma and IL-12. J Immunol. 1998;161:868–876.
    1. Yang Y, Xiang Z, Ertl HC, Wilson JM. Upregulation of class I major histocompatibility complex antigens by interferon gamma is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo. Proc Natl Acad Sci USA. 1995;92:7257–7261. doi: 10.1073/pnas.92.16.7257.
    1. Welsh RM, Che JW, Brehm MA, Selin LK. Heterologous immunity between viruses. Immunol Rev. 2010;235:244–266. doi: 10.1111/j.0105-2896.2010.00897.x.
    1. Messina NL, Zimmermann P, Curtis N. The impact of vaccines on heterologous adaptive immunity. Clin Microbiol Infect. 2019;25:1484–1493. doi: 10.1016/j.cmi.2019.02.016.
    1. Marino J, Paster J, Benichou G. Allorecognition by T lymphocytes and allograft rejection. Front Immunol. 2016;7:582. doi: 10.3389/fimmu.2016.00582.
    1. Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009;33:525–538. doi: 10.1016/j.leukres.2008.08.017.
    1. Har-Noy M, Zeira M, Weiss L, Slavin S. Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity. Leuk Res. 2008;32:1903–1913. doi: 10.1016/j.leukres.2008.05.007.
    1. Har-Noy M, Sukeepaisarnjaroen W, Lausoontornsiri W, Wittenberg A, Bloch M, Sonnenfeld T, Fingerut E, Kaminer Y, Ahooja A, Wongwiwatchai J, et al. Individualized cancer vaccine to elicit tumor debulking immunity in advanced HCC. J Clin Oncol. 2018;36:e15054. doi: 10.1200/JCO.2018.36.15_suppl.e15054.
    1. Har-Noy M, Lausoontornsiri W, Or R, Katsanis E. Response of HER2+ breast cancer patients to allogeneic cell immunotherapy. J Clin Oncol. 2012;30:e13013. doi: 10.1200/jco.2012.30.15_suppl.e13013.
    1. Epple LM, Bemis LT, Cavanaugh RP, Skope A, Mayer-Sonnenfeld T, Frank C, Olver CS, Lencioni AM, Dusto NL, Tal A, et al. Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine. Int J Hyperth. 2013;29:390–398. doi: 10.3109/02656736.2013.800997.
    1. Mayer-Sonnenfeld T, Har-Noy M, Lillehei KO, Graner MW. Proteomic analyses of different human tumour-derived chaperone-rich cell lysate (CRCL) anti-cancer vaccines reveal antigen content and strong similarities amongst the vaccines along with a basis for CRCL’s unique structure: CRCL vaccine proteome leads to unique structure. Int J Hyperth. 2013;29:520–527. doi: 10.3109/02656736.2013.796529.
    1. LaCasse CJ, Janikashvili N, Larmonier CB, Alizadeh D, Hanke N, Kartchner J, Situ E, Centuori S, Har-Noy M, Bonnotte B, et al. Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-gamma-dependent mechanism. J Immunol. 2011;187:6310–6317. doi: 10.4049/jimmunol.1101812.
    1. Janikashvili N, LaCasse CJ, Larmonier C, Trad M, Herrell A, Bustamante S, Bonnotte B, Har-Noy M, Larmonier N, Katsanis E. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia. Blood. 2011;117:1555–1564. doi: 10.1182/blood-2010-06-288621.
    1. Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70:1186–1192. doi: 10.1016/j.mehy.2007.10.008.
    1. Richters CD, Hoekstra MJ, du Pont JS, Kreis RW, Kamperdijk EW. Immunology of skin transplantation. Clin Dermatol. 2005;23:338–342. doi: 10.1016/j.clindermatol.2004.07.022.
    1. Bangs SC, Baban D, Cattan HJ, Li CK, McMichael AJ, Xu XN. Human CD4+ memory T cells are preferential targets for bystander activation and apoptosis. J Immunol. 2009;182:1962–1971. doi: 10.4049/jimmunol.0802596.
    1. Eberl G, Brawand P, MacDonald HR. Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation. J Immunol. 2000;165:4305–4311. doi: 10.4049/jimmunol.165.8.4305.
    1. Manser AR, Uhrberg M. Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance. Cancer Immunol Immunother. 2016;65:417–426. doi: 10.1007/s00262-015-1750-0.
    1. Liu W, Xiao X, Demirci G, Madsen J, Li XC. Innate NK cells and macrophages recognize and reject allogeneic nonself in vivo via different mechanisms. J Immunol. 2012;188:2703–2711. doi: 10.4049/jimmunol.1102997.
    1. Benichou G, Yamada Y, Yun SH, Lin C, Fray M, Tocco G. Immune recognition and rejection of allogeneic skin grafts. Immunotherapy. 2011;3:757–770. doi: 10.2217/imt.11.2.
    1. Ongradi J, Kovesdi V. Factors that may impact on immunosenescence: an appraisal. Immun Ageing. 2010;7:7. doi: 10.1186/1742-4933-7-7.
    1. Targonski PV, Jacobson RM, Poland GA. Immunosenescence: role and measurement in influenza vaccine response among the elderly. Vaccine. 2007;25:3066–3069. doi: 10.1016/j.vaccine.2007.01.025.
    1. Ongradi J, Stercz B, Kovesdi V, Vertes L. Immunosenescence and vaccination of the elderly, I. Age-related immune impairment. Acta Microbiol Immunol Hung. 2009;56:199–210. doi: 10.1556/AMicr.56.2009.3.1.
    1. Falsey AR, Walsh EE. Respiratory syncytial virus infection in elderly adults. Drugs Aging. 2005;22:577–587. doi: 10.2165/00002512-200522070-00004.
    1. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352:1749–1759. doi: 10.1056/NEJMoa043951.
    1. Saxena AK, Panhotra BR. The vulnerability of middle-aged and elderly patients to hepatitis C virus infection in a high-prevalence hospital-based hemodialysis setting. J Am Geriatr Soc. 2004;52:242–246. doi: 10.1111/j.1532-5415.2004.52062.x.
    1. Butt AA, Dascomb KK, DeSalvo KB, Bazzano L, Kissinger PJ, Szerlip HM. Human immunodeficiency virus infection in elderly patients. South Med J. 2001;94:397–400. doi: 10.1097/00007611-200194040-00008.
    1. Marcus EL, Tur-Kaspa R. Epidemiology of hepatitis C virus infection in the elderly. Gerontology. 2001;47:117–118. doi: 10.1159/000052783.
    1. Brunner S, Herndler-Brandstetter D, Weinberger B, Grubeck-Loebenstein B. Persistent viral infections and immune aging. Ageing Res Rev. 2011;10:362–369. doi: 10.1016/j.arr.2010.08.003.
    1. Haq K, McElhaney JE. Ageing and respiratory infections: the airway of ageing. Immunol Lett. 2014;162:323–328. doi: 10.1016/j.imlet.2014.06.009.
    1. Pawelec G, Adibzadeh M, Solana R, Beckman I. The T cell in the ageing individual. Mech Ageing Dev. 1997;93:35–45. doi: 10.1016/S0047-6374(96)01812-X.
    1. Katz AE. Immunity and aging. Otolaryngol Clin N Am. 1982;15:287–292.
    1. Gonzalez PA, Bueno SM, Riedel CA, Kalergis AM. Impairment of T cell immunity by the respiratory syncytial virus: targeting virulence mechanisms for therapy and prophylaxis. Curr Med Chem. 2009;16:4609–4625. doi: 10.2174/092986709789760724.
    1. Ma Y, Fang M. Immunosenescence and age-related viral diseases. Sci China Life Sci. 2013;56:399–405. doi: 10.1007/s11427-013-4478-0.
    1. Bektas A, Schurman SH, Sen R, Ferrucci L. Human T cell immunosenescence and inflammation in aging. J Leukoc Biol. 2017;102:977–988. doi: 10.1189/jlb.3RI0716-335R.
    1. Pera A, Campos C, Lopez N, Hassouneh F, Alonso C, Tarazona R, Solana R. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015;82:50–55. doi: 10.1016/j.maturitas.2015.05.004.
    1. Sun Y, Lopez CB. The innate immune response to RSV: advances in our understanding of critical viral and host factors. Vaccine. 2017;35:481–488. doi: 10.1016/j.vaccine.2016.09.030.
    1. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, Pan P, Wang W, Hu D, Liu X, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92:424–432. doi: 10.1002/jmv.25685.
    1. Rink L, Cakman I, Kirchner H. Altered cytokine production in the elderly. Mech Ageing Dev. 1998;102:199–209. doi: 10.1016/S0047-6374(97)00153-X.
    1. Shearer GM. Th1/Th2 changes in aging. Mech Ageing Dev. 1997;94:1–5. doi: 10.1016/S0047-6374(96)01849-0.
    1. Deng Y, Jing Y, Campbell AE, Gravenstein S. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol. 2004;172:3437–3446. doi: 10.4049/jimmunol.172.6.3437.
    1. Karanfilov CI, Liu B, Fox CC, Lakshmanan RR, Whisler RL. Age-related defects in Th1 and Th2 cytokine production by human T cells can be dissociated from altered frequencies of CD45RA+ and CD45RO+ T cell subsets. Mech Ageing Dev. 1999;109:97–112. doi: 10.1016/S0047-6374(99)00030-5.
    1. Akbar AN, Fletcher JM. Memory T cell homeostasis and senescence during aging. Curr Opin Immunol. 2005;17:480–485. doi: 10.1016/j.coi.2005.07.019.
    1. Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, et al. The immune system in extreme longevity. Exp Gerontol. 2008;43:61–65. doi: 10.1016/j.exger.2007.06.008.
    1. Saeidi A, Zandi K, Cheok YY, Saeidi H, Wong WF, Lee CYQ, Cheong HC, Yong YK, Larsson M, Shankar EM. T-cell exhaustion in chronic infections: reversing the state of exhaustion and reinvigorating optimal protective immune responses. Front Immunol. 2018;9:2569. doi: 10.3389/fimmu.2018.02569.
    1. Henson SM, Akbar AN. Memory T-cell homeostasis and senescence during aging. Adv Exp Med Biol. 2010;684:189–197. doi: 10.1007/978-1-4419-6451-9_15.
    1. Minato N, Hattori M, Hamazaki Y. Physiology and pathology of T-cell aging. Int Immunol. 2020;32:223–231. doi: 10.1093/intimm/dxaa006.
    1. Lepletier A, Alsharif A, Chidgey AP. Inflammation and thymus ageing. Front Horm Res. 2017;48:19–36. doi: 10.1159/000452903.
    1. Dugan HL, Henry C, Wilson PC. Aging and influenza vaccine-induced immunity. Cell Immunol. 2020;348:103998. doi: 10.1016/j.cellimm.2019.103998.
    1. Sharma G, Goodwin J. Effect of aging on respiratory system physiology and immunology. Clin Interv Aging. 2006;1:253–260. doi: 10.2147/ciia.2006.1.3.253.
    1. Oh SJ, Lee JK, Shin OS. Aging and the immune system: the impact of immunosenescence on viral infection, immunity and vaccine immunogenicity. Immune Netw. 2019;19:e37. doi: 10.4110/in.2019.19.e37.
    1. Szucs T. The socio-economic burden of influenza. J Antimicrob Chemother. 1999;44(Suppl B):11–15. doi: 10.1093/jac/44.suppl_2.11.
    1. Maynard A, Bloor K. The economic impact of pandemic influenza. BMJ. 2009;339:b4888. doi: 10.1136/bmj.b4888.
    1. Roses M, Bonvehi PE. Vaccines in adults. Medicina (B Aires) 2019;79:552–558.
    1. Crooke SN, Ovsyannikova IG, Poland GA, Kennedy RB. Immunosenescence and human vaccine immune responses. Immun Ageing. 2019;16:25. doi: 10.1186/s12979-019-0164-9.
    1. Hakim FT, Flomerfelt FA, Boyiadzis M, Gress RE. Aging, immunity and cancer. Curr Opin Immunol. 2004;16:151–156. doi: 10.1016/j.coi.2004.01.009.
    1. Muller L, Di Benedetto S, Pawelec G. The immune system and its dysregulation with aging. Subcell Biochem. 2019;91:21–43. doi: 10.1007/978-981-13-3681-2_2.
    1. Sadighi Akha AA. Aging and the immune system: an overview. J Immunol Methods. 2018;463:21–26. doi: 10.1016/j.jim.2018.08.005.
    1. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*) Annu Rev Immunol. 2010;28:445–489. doi: 10.1146/annurev-immunol-030409-101212.
    1. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem. 1998;67:227–264. doi: 10.1146/annurev.biochem.67.1.227.
    1. Wagner A, Garner-Spitzer E, Jasinska J, Kollaritsch H, Stiasny K, Kundi M, Wiedermann U. Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules. Sci Rep. 2018;8:9825. doi: 10.1038/s41598-018-28111-8.
    1. Lau SKP, Lau CCY, Chan KH, Li CPY, Chen H, Jin DY, Chan JFW, Woo PCY, Yuen KY. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol. 2013;94:2679–2690. doi: 10.1099/vir.0.055533-0.
    1. Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, Perlman S. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19:181–193. doi: 10.1016/j.chom.2016.01.007.
    1. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39:529–539. doi: 10.1007/s00281-017-0629-x.
    1. Kang S, Brown HM, Hwang S. Direct antiviral mechanisms of interferon-gamma. Immune Netw. 2018;18:e33. doi: 10.4110/in.2018.18.e33.
    1. Shrestha B, Wang T, Samuel MA, Whitby K, Craft J, Fikrig E, Diamond MS. Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection. J Virol. 2006;80:5338–5348. doi: 10.1128/JVI.00274-06.
    1. Levy DE, Garcia-Sastre A. The virus battles: IFN induction of the antiviral state and mechanisms of viral evasion. Cytokine Growth Factor Rev. 2001;12:143–156. doi: 10.1016/S1359-6101(00)00027-7.
    1. Gaajetaan GR, Geelen TH, Vernooy JH, Dentener MA, Reynaert NL, Rohde GG, Beuken EV, Grauls GE, Bruggeman CA, Stassen FR. Interferon-beta induces a long-lasting antiviral state in human respiratory epithelial cells. J Infect. 2013;66:163–169. doi: 10.1016/j.jinf.2012.11.008.
    1. Aizaki H, Saito S, Ogino T, Miyajima N, Harada T, Matsuura Y, Miyamura T, Kohase M. Suppression of interferon-induced antiviral activity in cells expressing hepatitis C virus proteins. J Interferon Cytokine Res. 2000;20:1111–1120. doi: 10.1089/107999000750053780.
    1. Guo P. Suppression of interferon-mediated antiviral immunity by hepatitis B virus: an overview of research progress. Scand J Immunol. 2013;78:230–237. doi: 10.1111/sji.12086.
    1. Comar CE, Goldstein SA, Li Y, Yount B, Baric RS, Weiss SR. Antagonism of dsRNA-induced innate immune pathways by NS4a and NS4b accessory proteins during MERS coronavirus infection. mBio. 2019;10:e00319-19. doi: 10.1128/mBio.00319-19.
    1. Siu KL, Chan CP, Kok KH, Chiu-Yat Woo P, Jin DY. Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain. Cell Mol Immunol. 2014;11:141–149. doi: 10.1038/cmi.2013.61.
    1. Romeo G, Affabris E, Federico M, Mechti N, Coccia EM, Jemma C, Rossi GB. Establishment of the antiviral state in alpha, beta-interferon-resistant Friend cells treated with gamma-interferon. Induction of 67-kilodalton protein kinase activity in absence of detectable 2-5A synthetase. J Biol Chem. 1985;260:3833–3838.
    1. Anderson MJ. The role of interferon in the NK cell killing of virus-infected target cells. J Hyg. 1982;89:347–351. doi: 10.1017/S0022172400070881.
    1. Pawelec G. Immunosenescence and cancer. Biogerontology. 2017;18:717–721. doi: 10.1007/s10522-017-9682-z.
    1. Zanussi S, Serraino D, Dolcetti R, Berretta M, De Paoli P. Cancer, aging and immune reconstitution. Anticancer Agents Med Chem. 2013;13:1310–1324. doi: 10.2174/18715206113136660348.
    1. Yu HT, Park S, Shin EC, Lee WW. T cell senescence and cardiovascular diseases. Clin Exp Med. 2016;16:257–263. doi: 10.1007/s10238-015-0376-z.
    1. Costantini E, D’Angelo C, Reale M. The role of immunosenescence in neurodegenerative diseases. Mediat Inflamm. 2018;2018:6039171.
    1. Solana C, Tarazona R, Solana R. Immunosenescence of natural killer cells, inflammation, and alzheimer’s disease. Int J Alzheimers Dis. 2018;2018:3128758.
    1. Whary MT, Fox JG. Th1-mediated pathology in mouse models of human disease is ameliorated by concurrent Th2 responses to parasite antigens. Curr Top Med Chem. 2004;4:531–538. doi: 10.2174/1568026043451276.
    1. Strober W, Kelsall B, Fuss I, Marth T, Ludviksson B, Ehrhardt R, Neurath M. Reciprocal IFN-gamma and TGF-beta responses regulate the occurrence of mucosal inflammation. Immunol Today. 1997;18:61–64. doi: 10.1016/S0167-5699(97)01000-1.
    1. Witkowski JM, Bryl E, Fulop T. Should we try to alleviate immunosenescence and inflammaging—why, how and to what extent? Curr Pharm Des. 2019;25:4154–4162. doi: 10.2174/1381612825666191111153016.
    1. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, Law KI, Tang BS, Hon TY, Chan CS, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361:1767–1772. doi: 10.1016/S0140-6736(03)13412-5.
    1. Chien JY, Hsueh PR, Cheng WC, Yu CJ, Yang PC. Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome. Respirology. 2006;11:715–722. doi: 10.1111/j.1440-1843.2006.00942.x.
    1. Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, Muller MP, Gold WL, Richardson SE, Poutanen SM, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007;81:8692–8706. doi: 10.1128/JVI.00527-07.
    1. Oldstone MB, Rosen H. Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule. Curr Top Microbiol Immunol. 2014;378:129–147.
    1. Monneret G, Gossez M, Venet F. Sepsis and immunosenescence: closely associated in a vicious circle. Aging Clin Exp Res. 2019 doi: 10.1007/s40520-019-01350-z.
    1. Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing sepsis as a global health priority—a WHO resolution. N Engl J Med. 2017;377:414–417. doi: 10.1056/NEJMp1707170.
    1. Bauer TT, Ewig S, Rodloff AC, Muller EE. Acute respiratory distress syndrome and pneumonia: a comprehensive review of clinical data. Clin Infect Dis. 2006;43:748–756. doi: 10.1086/506430.
    1. Joynt GM, Yap HY. SARS in the intensive care unit. Curr Infect Dis Rep. 2004;6:228–233. doi: 10.1007/s11908-004-0013-6.
    1. Isobe KI, Nishio N, Hasegawa T. Immunological aspects of age-related diseases. World J Biol Chem. 2017;8:129–137. doi: 10.4331/wjbc.v8.i2.129.
    1. Kale SS, Yende S. Effects of aging on inflammation and hemostasis through the continuum of critical illness. Aging Dis. 2011;2:501–511.
    1. Alves AS, Bueno V. Immunosenescence: participation of T lymphocytes and myeloid-derived suppressor cells in aging-related immune response changes. Einstein. 2019;17:eRB4733. doi: 10.31744/einstein_journal/2019RB4733.
    1. Hurez V, Daniel BJ, Sun L, Liu AJ, Ludwig SM, Kious MJ, Thibodeaux SR, Pandeswara S, Murthy K, Livi CB, et al. Mitigating age-related immune dysfunction heightens the efficacy of tumor immunotherapy in aged mice. Cancer Res. 2012;72:2089–2099. doi: 10.1158/0008-5472.CAN-11-3019.
    1. Salminen A, Kaarniranta K, Kauppinen A. Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency. Cell Mol Life Sci. 2019;76:1901–1918. doi: 10.1007/s00018-019-03048-x.
    1. Venet F, Demaret J, Gossez M, Monneret G. Myeloid cells in sepsis-acquired immunodeficiency. Ann N Y Acad Sci. 2020 doi: 10.1111/nyas.14333.
    1. Netherby CS, Abrams SI. Mechanisms overseeing myeloid-derived suppressor cell production in neoplastic disease. Cancer Immunol Immunother. 2017;66:989–996. doi: 10.1007/s00262-017-1963-5.
    1. Gonda K, Shibata M, Ohtake T, Matsumoto Y, Tachibana K, Abe N, Ohto H, Sakurai K, Takenoshita S. Myeloid-derived suppressor cells are increased and correlated with type 2 immune responses, malnutrition, inflammation, and poor prognosis in patients with breast cancer. Oncol Lett. 2017;14:1766–1774. doi: 10.3892/ol.2017.6305.
    1. Nam S, Kang K, Cha JS, Kim JW, Lee HG, Kim Y, Yang Y, Lee MS, Lim JS. Interferon regulatory factor 4 (IRF4) controls myeloid-derived suppressor cell (MDSC) differentiation and function. J Leukoc Biol. 2016;100:1273–1284. doi: 10.1189/jlb.1A0215-068RR.
    1. Medina-Echeverz J, Haile LA, Zhao F, Gamrekelashvili J, Ma C, Metais JY, Dunbar CE, Kapoor V, Manns MP, Korangy F, Greten TF. IFN-gamma regulates survival and function of tumor-induced CD11b+ Gr-1high myeloid derived suppressor cells by modulating the anti-apoptotic molecule Bcl2a1. Eur J Immunol. 2014;44:2457–2467. doi: 10.1002/eji.201444497.

Source: PubMed

3
Prenumerera