Frontiers in immunology · 2025
Therapeutic mucosal vaccination of herpes simplex virus type 2 infected guinea pigs with an adenovirus-based vaccine expressing the ribonucleotide reductase 2 and glycoprotein D induces local tissue-resident CD4+ and CD8+ TRM cells associated with protection against recurrent genital herpes.
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Quadiri Afshana, Prakash Swayam, Vahed Hawa, Tadros Jimmy Medhat, Sun Miyo, Hormi-Carver Kathy K, Patel Swena Jignesh, BenMohamed Lbachir
Аннотация
INTRODUCTION: The reactivation of herpes simplex virus 2 (HSV-2) from latency causes viral shedding that develops into recurrent genital lesions. The role of tissue-resident T cells and the nature of viral antigens associated with protection against recurrent genital herpes remain to be fully elucidated.
METHODS: In this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of five recombinant adenovirus-based therapeutic vaccine candidates (rAd-Ags), each expressing different HSV-2 envelope and tegument proteins: RR1 (UL39), RR2 (UL40), gD (glycoprotein D), VP16 (UL48), or VP22 (UL49). We compared the frequency and function of dorsal root ganglia (DRG)- and vaginal mucosa (VM)-resident CD4+ and CD8+ T cells induced by each vaccine and their effect on the frequency and severity of recurrent genital herpes.
RESULTS: HSV-2 latent-infected guinea pigs immunized with rAd-RR2 and rAd-gD vaccines showed high frequencies of DRG- and VM-tissue-resident IFN-g-producing CD4+ and CD8+ TRM cells associated with significant reductions in viral shedding and genital herpetic lesions.
DISCUSSION: Taken together, these preclinical results provide new insights into the T cell mechanisms of protection against recurrent genital herpes and confirm the tegument RR2 protein and glycoprotein D as viable candidate antigens to be incorporated in future genital herpes therapeutic vaccines.
METHODS: In this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of five recombinant adenovirus-based therapeutic vaccine candidates (rAd-Ags), each expressing different HSV-2 envelope and tegument proteins: RR1 (UL39), RR2 (UL40), gD (glycoprotein D), VP16 (UL48), or VP22 (UL49). We compared the frequency and function of dorsal root ganglia (DRG)- and vaginal mucosa (VM)-resident CD4+ and CD8+ T cells induced by each vaccine and their effect on the frequency and severity of recurrent genital herpes.
RESULTS: HSV-2 latent-infected guinea pigs immunized with rAd-RR2 and rAd-gD vaccines showed high frequencies of DRG- and VM-tissue-resident IFN-g-producing CD4+ and CD8+ TRM cells associated with significant reductions in viral shedding and genital herpetic lesions.
DISCUSSION: Taken together, these preclinical results provide new insights into the T cell mechanisms of protection against recurrent genital herpes and confirm the tegument RR2 protein and glycoprotein D as viable candidate antigens to be incorporated in future genital herpes therapeutic vaccines.