Therapeutic Mucosal Vaccination of Herpes Simplex Virus 2-Infected Guinea Pigs with Ribonucleotide Reductase 2 (RR2) Protein Boosts Antiviral Neutralizing Antibodies and Local Tissue-Resident CD4+ and CD8+ TRM Cells Associated with Protection against Recurrent Genital Herpes

Journal of Virology
Ruchi SrivastavaLbachir BenMohamed

Abstract

Reactivation of herpes simplex virus 2 (HSV-2) from latency causes viral shedding that develops into recurrent genital lesions. The immune mechanisms of protection against recurrent genital herpes remain to be fully elucidated. In this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed HSV-2 envelope and tegument proteins. These viral protein antigens (Ags) were rationally selected for their ability to recall strong CD4+ and CD8+ T-cell responses from naturally "protected" asymptomatic individuals, who, despite being infected, never develop any recurrent herpetic disease. Out of the eight HSV-2 proteins, the envelope glycoprotein D (gD), the tegument protein VP22 (encoded by the UL49 gene), and ribonucleotide reductase subunit 2 protein (RR2; encoded by the UL40 gene) produced significant protection against recurrent genital herpes. The RR2 protein, delivered either intramuscularly or intravaginally with CpG and alum adjuvants, (i) boosted the highest neutralizing antibodies, which appear to cross-react with both gB and gD, and (ii) enhanced the numbers of functional gamma inte...Continue Reading

References

Apr 1, 1992·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·T A Banks, B T Rouse
Dec 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aziz Alami ChentoufiLbachir BenMohamed
Aug 1, 2008·Clinical and Vaccine Immunology : CVI·Xiuli ZhangLbachir BenMohamed
Sep 19, 2008·Journal of Virology·Aziz Alami ChentoufiLbachir BenMohamed
Jul 25, 2009·Expert Review of Vaccines·Gargi DasguptaLbachir BenMohamed
Dec 22, 2009·Future Microbiology·Gargi DasguptaLbachir BenMohamed
Jul 17, 2010·Journal of Clinical Immunology·Kerry J LaingLawrence Corey
Jul 9, 2011·Nature Immunology·E John Wherry
Jul 19, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amol SuryawanshiBarry T Rouse
Dec 3, 2011·The Journal of Clinical Investigation·Christine JohnstonAnna Wald
Jan 6, 2012·The New England Journal of Medicine·Robert B BelsheUNKNOWN Herpevac Trial for Women
May 2, 2012·Clinical & Developmental Immunology·Aziz Alami ChentoufiLbachir Benmohamed
Jun 16, 2012·Future Virology·Xavier DervillezLbachir Benmohamed
Sep 29, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiuli ZhangLbachir Benmohamed
Dec 21, 2012·Expert Review of Vaccines·Lesia K Dropulic, Jeffrey I Cohen
Jan 16, 2013·Clinical & Developmental Immunology·Aziz Alami Chentoufi, Lbachir Benmohamed
Jan 18, 2013·Clinical & Developmental Immunology·Aziz Alami ChentoufiAli A Ashkar
Apr 29, 2015·The New England Journal of Medicine·Himal LalUNKNOWN ZOE-50 Study Group
Oct 16, 2015·The New England Journal of Medicine·Himal LalThomas C Heineman
Oct 16, 2015·The New England Journal of Medicine·Ige A George, Steven J Lawrence
Oct 16, 2015·The New England Journal of Medicine·James E Fielding, Stephen B Lambert

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Citations

Jun 18, 2020·Vaccines·Anthony C IkeSophia O Muo
Jul 24, 2021·Expert Review of Vaccines·Vindya Nilakshi WijesingheSunil Kumar Lal

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