Efficacy of genital T cell responses to herpes simplex virus type 2 resulting from immunization of the nasal mucosa

Abstract

Intravaginal (ivag) or intranasal (i.n.) immunization of C57BL/6J (B6) mice with a thymidine kinase-deficient strain (tk-) of herpes simplex virus type 2 (HSV-2) resulted in comparable protection of the genital epithelium and sensory ganglia against HSV-2 challenge. In contrast, protection of these sites was much reduced in i.n.-immunized compared to ivag-immunized B cell-deficient microMT mice. Fewer HSV-specific T cells were detected in the genital epithelium of i.n.-immunized compared to ivag-immunized microMT mice after HSV-2 challenge. Passive transfer of HSV-specific serum to immune microMT mice restored protection of these sites against HSV-2 challenge. These results suggest that protection of genital and neuronal sites may be conferred by i.n. immunization but may be more dependent on antibody-dependent mechanisms than the protection resulting from genital immunization. These results have implications for immunization strategies to elicit high levels of cell-mediated protection of the genital tract and sensory ganglia.

Vaginal Memory T Cells Induced by Intranasal Vaccination Are Critical for Protective T Cell Recruitment and Prevention of Genital HSV-2 Disease

“…As previously reported (17,26), mice immunized i.n. with HSV-2 TK Ϫ survived without serious genital inflammation in the face of challenge with IVAG WT HSV-2 ( Fig.…”

“…immunization is an effective vaccine strategy against STDs, such as human immunodeficiency virus and HSV, because it can effectively induce Ag-specific immune responses in the distant vaginal mucosa (16,17). For instance, Ag-specific Ab responses and protective immunity in the vaginal mucosa are induced more effectively by i.n.…”

“…immunization with HSV-2 TK Ϫ induces the production of HSV-2-specific gamma interferon (IFN-␥)-secreting cells in both the vaginal tract and the draining lymph nodes (dLNs). Subsequent intravaginal (IVAG) wild-type (WT) HSV-2 challenge then induces protective immunity in the genital tract and sensory ganglia at levels comparable to those from IVAG immunization with the same attenuated virus (17). However, the precise cellular mechanisms by which i.n.…”

Effector CD4+T-Cell Involvement in Clearance of Infectious Herpes Simplex Virus Type 1 from Sensory Ganglia and Spinal Cords

“…HSV-1 strain SC16 was obtained from Lawrence Stanberry (Columbia University, New York, NY). Virus stocks were prepared by infection of Vero cell monolayers at a multiplicity of infection of 0.01, as previously described (40,41). The virus was released from the Vero cells by three freeze-thaw cycles (40,41).…”

Adaptive immune responses fail to provide protection against genital HSV‐2 infection in the absence of IL‐15

“…The second is the induced innate immune response carried out by NK/NKT cells and IFN-c and can occur 24-72 h post viral infection. Finally, the adaptive immune response, which usually takes at least 5-7 days to be functional [8][9][10][11], is initiated. It is now well established that the adaptive immune response is critical in the clearance of viral infections.…”