2022, Number 1
<< Back Next >>
MEDICC Review 2022; 24 (1)
Innate immune stimulation should not be overlooked in post-exposure prophylaxis and early therapy for coronavirus infections
Aguilar-Rubido JC, Pentón-Arias E, Fazle Akbar SM
Language: English
References: 36
Page: 70-75
PDF size: 217.71 Kb.
ABSTRACT
We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus’ entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.
REFERENCES
Kikkert M. Innate immune evasion by humanrespiratory RNA viruses. J Innate Immun. 2020Jan–Feb;12(1):4–20.
Metcalf TU, Cubas RA, Ghneim K, CartwrightMJ, Grevenynghe JV, Richner JM, et al. Globalanalyses revealed age-related alterations ininnate immune responses after stimulation ofpathogen recognition receptors. Aging Cell. 2015Jun;14(3):421–32.
Neumann-Podczaska A, Al-Saad SR, KarbowskiLM, Chojnicki M, Tobis S, Wieczorowska-Tobis K.COVID 19 - Clinical picture in the elderly population:a qualitative systematic review. Aging Dis.2020 Jul 23;11(4):988–1008.
Kumaki Y, Salazar AM, Wandersee MK, BarnardDL. Prophylactic and therapeutic intranasaladministration with an immunomodulator,Hiltonol® (Poly IC:LC), in a lethal SARS-CoVinfectedBALB/c mouse model. Antiviral Res.2017 Mar;139:1–12.
Zhao J, Wohlford-Lenane C, Zhao J, Fleming E,Lane TE, McCray PB Jr, et al. Intranasal treatmentwith poly(I•C) protects aged mice fromlethal respiratory virus infections. J Virol. 2012Nov;86(21):11416–24.
Pentón-Arias E, Aguilar-Rubido JC. Cubanprophylactic and therapeutic vaccines for controllinghepatitis B. MEDICC Rev [Internet].2021 Jan [cited 2021 Feb 7];23(1):21–9. DOI:10.37757/MR2021.V23.N1.6. Available at:https://mediccreview.org/estadisticas/ppp.php?y=2021&v=1&p=21
Al-Mahtab M, Akbar SM, Aguilar JC, Uddin MH,Khan MS, Rahman S. Therapeutic potential of acombined hepatitis B virus surface and core antigenvaccine in patients with chronic hepatitis B.Hepatol Int. 2013 Oct;7(4):981–9.
Akbar SMF, Yoshida O, Chen S, Cesar AJ, AbeM, Matsuura B, et al. Immune modulator andantiviral potential of dendritic cells pulsed withboth hepatitis B surface antigen and core antigenfor treating chronic HBV infection. Antivir Ther.2010;15(6):887–95.
Lobaina Y, Hardtke S, Wedemeyer H, Aguilar JC,Schlaphoff V. In vitro stimulation with HBV therapeuticvaccine candidate Nasvac activates B and Tcells from chronic hepatitis B patients and healthydonors. Mol Immunol. 2015 Feb;63(2):320–7.
Aguilar JC, Lobaina Y, Muzio V, García D, PentónE, Iglesias E, et al. Development of a nasal vaccinefor chronic hepatitis B infection that uses the abilityof hepatitis B core antigen to stimulate a strongTh1 response against hepatitis B surface antigen.Immunol Cell Biol. 2004 Oct;82(5):539–46.
Fleites YA, Aguiar J, Cinza Z, Bequet-RomeroM, Marrero E, Vizcaíno M, et al. HeberNasvac, atherapeutic vaccine for chronic hepatitis B, stimulateslocal and systemic markers of innate immunity:potential use in SARS-CoV-2 post-exposureprophylaxis. Euroasian J Hepatogastroenterol.2021 Jul–Dec;11(2):59–70.
Clinical trials of HeberNasvac and Mambisaindexed at the Cuban Registry of Clinical Trials(RPCEC00000326-En; RPCEC00000353-En; RPCEC00000356-En; RPCEC00000345-En andRPCEC00000382-En) [Internet]. Havana:National Clinical Trials Coordinating Center –CENCEC (CU); c2020–2021 [cited 2021 Aug 21].Available at: https://rpcec.sld.cu/trials/. Spanish.
Akbar SMF, Mahtab MA, Aguilar JC, Uddin MH,Khan SI, Yoshida O, et al. Repurposing NASVAC,A Hepatitis B Therapeutic Vaccine, forpre-and post-exposure prophylaxis of SARSCoV-2 infection. J Antivir Antiretrovir. 2021May;13(S20):1000004.
Aguilar JC, Aguiar J, inventors; Center for GeneticEngineering and Biotechnology, assignee. Viralnucleoprotein and formulations thereof. Cuba patentapplication CU 2020-0028. 2020 April 20.
Aguilar JC. A therapeutic perspective of theimmunological function of the liver. Biotecnol Apl.2010 Jan;27(1):10–8.
Prasad K, Khatoon F, Rashid S, Ali N, A AsmariAF, Ahmed MZ, et al. Targeting hub genes andpathways of innate immune response in COVID-19: a network biology perspective. Int J BiolMacromol. 2020 Nov 15;163:1–8.
Aich P, Wilson HL, Kaushik RS, Potter AA, BabiukLA, Griebel P. Comparative analysis of innateimmune responses following infection of newborncalves with bovine rotavirus and bovine coronavirus.J Gen Virol. 2007 Oct;88(Pt 10):2749–61.
Zhu Q, Egelston C, Gagnon S, Sui Y, BelyakovIM, Klinman DM, et al. Using 3 TLR ligandsas a combination adjuvant induces qualitativechanges in T cell responses needed forantiviral protection in mice. J Clin Invest. 2010Feb;120(2):607–16.
Zhu Q, Egelston C, Vivekanandhan A, UematsuS, Akira S, Klinman DM, et al. Toll-like receptorligands synergize through distinct dendritic cellpathways to induce T cell responses: implicationsfor vaccines. Proc Natl Acad Sci U S A. 2008 Oct;105(42):16260–5.
Cooper A, Tal G, Lider O, Shaul Y. Cytokineinduction by the hepatitis B virus capsid in macrophagesis facilitated by membrane heparansulfate and involves TLR2. J Immunol. 2005Sep;175(5):3165–76.
Lee BO, Tucker A, Frelin L, Sallberg M, JonesJ, Peters C, et al. Interaction of the hepatitis Bcore antigen and the innate immune system. JImmunol. 2009 Jun;182(11):6670–81.
Mao T, Israelow B, Lucas C, Vogels CBF, FedorovaO, Breban MI, et al. A stem-loop RNA RIG-Iagonist confers prophylactic and therapeutic protectionagainst acute and chronic SARS-CoV-2infection in mice. bioRxiv 448754 [Preprint]. 2021Jun 17 [cited 2021 Jun 26]. Available at: https://doi.org/10.1101/2021.06.16.448754
Thorne LG, Bouhaddou M, Reuschl AK, Zuliani-Alvarez L, Polacco B, Pelin A, et al. Evolution ofenhanced innate immune evasion by the SARSCoV-2 B.1.1.7 UK variant. bioRxiv 446826 [Preprint].2021 Jun 7 [cited 2021 Jun 16]. Availableat: https://doi.org/10.1101/2021.06.06.446826.
Curtis N, Sparrow A, Ghebreyesus TA, NeteaMG. Considering BCG vaccination to reducethe impact of COVID-19. Lancet. 2020May;395(10236):1545–6.
Iturriaga C, Eiffl er N, Aniba R, Ben-Othman R,Perez-Mateluna G, Meyer JKV, et al. A clusterrandomized trial of interferon ß-1a for thereduction of transmission of SARS-Cov-2: protocolfor the Containing Coronavirus Disease 19trial (ConCorD-19). BMC Infect Dis. 2021 Aug13;21(1):814.
Nasalferon [Recombinant Human InterferonAlpha 2b]. Summary of Product Features.[Internet]. Havana: Center for State Control ofMedicines, Equipment and Medical Devices -CECMED (CU) ; c2021 [cited 2021 Aug 21].Available at: https://www.cecmed.cu/registro/rcp/nasalferon-Interferon-alfa-2b-humano-recombinante. Spanish.
Pereda R, González D, Blas Rivero H, RiveroJC, Pérez A, Del Rosario López L, et al. Therapeuticeff ectiveness of interferon-α2b againstCOVID-19: the Cuban experience. J InterferonCytokine Res. 2020 Sep;40(9):438–42.
Sánchez Ramón S, Manzanares M, CandelasG. MUCOSAL anti-infections vaccines: beyondconventional vaccines. Reumatol Clin (Engl Ed).2020 Jan–Feb;16(1):49–55. English, Spanish.
Altimmune Receives Award from U.S. Departmentof Defense to Fund Phase 1/2 Clinical Trialof T-COVID™ in Outpatients with Early COVID-19 [Internet]. Gaithersburg: Altimmune Headquarters;2020 Jun 29 [cited 2021 Jun 29]; [about2 p.]. Available at: https://www.globenewswire.com/news-release/2020/06/29/2054563/0/en/Altimmune-Receives-Award-from-U-S-Department-of-Defense-to-Fund-Phase-1-2-Clinical-Trial-of-T-COVID-in-Outpatients-with-Early-COVID-19.html
Arunachalam PS, Wimmers F, Mok CKP, PereraRAPM, Scott M, Hagan T, et al. Systems biologicalassessment of immunity to mild versussevere COVID-19 infection in humans. Science.2020 Sep 4;369(6508):1210–20.
Sariol CA, Martínez MI, Rivera F, RodríguezIV, Pantoja P, Abel K, et al. Decreased denguereplication and an increased anti-viral humoralresponse with the use of combined Toll-likereceptor 3 and 7/8 agonists in macaques. PLoSOne. 2011 Apr 29;6(4):e19323.
Yuan MM, Xu YY, Chen L, Li XY, Qin J, Shen Y.TLR3 expression correlates with apoptosis, proliferationand angiogenesis in hepatocellular carcinomaand predicts prognosis. BMC Cancer. 2015Apr 9;15:245. DOI: 10.1186/s12885-015-1262-5
Aguilar JC, Rodríguez EG. Vaccine adjuvantsrevisited. Vaccine. 2007 May 10;25(19):3752–62.
Sui Y, Berzofsky JA. Myeloid cell-mediated trainedinnate immunity in mucosal AIDS vaccine development.Front Immunol. 2020 Feb 28;11:315.DOI: 10.3389/fi mmu.2020.00315
Netea MG, Giamarellos-Bourboulis EJ, Domínguez-Andrés J, Curtis N, van Crevel R, van deVeerdonk FL, et al. Trained immunity: a toolfor reducing susceptibility to and the severityof SARS-CoV-2 infection. Cell. 2020 May28;181(5):969–77.
Iglesias E, Thompson R, Carrazana Y, Lobaina Y,García D, Sánchez J, et al. Coinoculation withhepatitis B surface and core antigen promotes aTh1 immune response to a multiepitopic protein ofHIV-1. Immunol Cell Biol. 2006 Apr;84(2):174–83.