Lymphokine Expression Profile of Resting and Stimulated CD4+ CTL Clones Specific for the Glycoprotein of Vesicular Stomatitis Virus

Cao, Ben Ning; Huneycutt, Brandon S.; Gapud, Carolina P.; Arceci, Robert J.; Reiss, Carol Shoshkes

doi:10.1006/cimm.1993.1013

Cited by 5 publications

(2 citation statements)

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“…The HSV-2 gD antigen has been demonstrated to elicit cytotoxic T cells that belong to the CD4 ϩ subset in both humans (69) and mice (9). The ability of rVSV vectors to produce Th1 CD4 ϩ effector cells directed against the inserted recombinant antigen correlates well with the natural immune responses generated against VSV infections (6,35).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4⁺Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Natuk

Cooper

Guo

et al. 2006

J Virol

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Recombinant vesicular stomatitis virus (rVSV) vectors offer an attractive approach for the induction of robust cellular and humoral immune responses directed against human pathogen target antigens. We evaluated rVSV vectors expressing full-length glycoprotein D (gD) from herpes simplex virus type 2 (HSV-2) in mice and guinea pigs for immunogenicity and protective efficacy against genital challenge with wild-type HSV-2. Robust Th1-polarized anti-gD immune responses were demonstrated in the murine model as measured by induction of gD-specific cytotoxic T lymphocytes and increased gamma interferon expression. The isotype makeup of the serum anti-gD immunoglobulin G (IgG) response was consistent with the presence of a Th1-CD4 ؉ anti-gD response, characterized by a high IgG2a/IgG1 IgG subclass ratio. Functional anti-HSV-2 neutralizing serum antibody responses were readily demonstrated in both guinea pigs and mice that had been immunized with rVSV-gD vaccines. Furthermore, guinea pigs and mice were prophylactically protected from genital challenge with high doses of wild-type HSV-2. In addition, guinea pigs were highly protected against the establishment of latent infection as evidenced by low or absent HSV-2 genome copies in dorsal root ganglia after virus challenge. In summary, rVSV-gD vectors were successfully used to elicit potent anti-gD Th1-like cellular and humoral immune responses that were protective against HSV-2 disease in guinea pigs and mice.Herpes simplex virus type 2 (HSV-2) infections remain a serious public health problem worldwide. HSV-2 genital lesions are not only painful and disfiguring but also facilitate the transmission of human immunodeficiency virus (HIV) (7). The seroprevalence in the United States has increased by 30% between 1976 and 1994, and roughly one of every five people over the age of 12 in the United States is infected with HSV-2 (15). Individuals latently infected with HSV-2 remain infected for life and can exhibit asymptomatic viral shedding. It is therefore believed that, without intervention, such as the development of prophylactic and/or therapeutic HSV-2 vaccines, HSV-2 prevalence will continue to rise in the future.Small experimental animal vaginal challenge models in mice and guinea pigs have been used for preclinical evaluation of a number of HSV-2 vaccine strategies, including subunit vaccines (gB and/or gD with or without interleukin-12 [IL-12]), plasmid HSV DNA vaccines (gD and/or gB with or without cytokine DNA (IL-2, IL-4, IL-10, IL-12, IL-15, or IL-18), attenuated HSV-2 vaccines (TKϪ, BlacZ, dl5-29, RAV 9395, ICP10⌬PK, or AD472), and virus-vectored HSV-2 vaccines (adenovirus, varicella-zoster virus, or vaccinia virus) (1,9,12,17,21,22, 34, 39, 40,45,60,62,66). Various degrees of success have been achieved in these preclinical studies, but limited success has carried over to the clinical setting, where the experience with HSV-2 subunit vaccines has had mixed results (10). Nonetheless, an adjuvanted gD subunit approach has achieved some success in early clinical trials...

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Section: Discussionmentioning

confidence: 99%

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4⁺Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Natuk

Cooper

Guo

et al. 2006

J Virol

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“…Furthermore, switching from the IgM to the IgG isotype is strictly dependent on T helper cells (18). Therefore, VSV-specific CD4 ϩ T cells might be mainly involved in the maintenance of a long-lasting immunity against VSV via local interleukin action but in addition may be involved in the recruitment of B cells into immunologically privileged sites (4,25,26).…”

Section: Discussionmentioning

confidence: 99%

Antiviral protection by vesicular stomatitis virus-specific antibodies in alpha/beta interferon receptor-deficient mice

Steinhoff

Müller

Schertler

et al. 1995

J Virol

123

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The role of innate, alpha/beta interferon (IFN-␣/␤)-dependent protection versus specific antibody-mediated protection against vesicular stomatitis virus (VSV) was evaluated in IFN-␣/␤ receptor-deficient mice (IFN-␣/␤ R 0 / 0 mice). VSV is a close relative to rabies virus that causes neurological disease in mice. In contrast to normal mice, IFN-␣/␤ R 0 / 0 mice were highly susceptible to infection with VSV because of ubiquitous high viral replication. Adoptive transfer experiments showed that neutralizing antibodies against the glycoprotein of VSV (VSV-G) protected these mice efficiently against systemic infection and against peripheral subcutaneous infection but protected only to a limited degree against intranasal infection with VSV. In contrast, VSV-specific T cells or antibodies specific for the nucleoprotein of VSV (VSV-N) were unable to protect IFN-␣/␤ R 0 / 0 mice against VSV. These results demonstrate that mice are extremely sensitive to VSV if IFN-␣/␤ is not functional and that under these conditions, neutralizing antibody responses mediate efficient protection, but apparently only against extraneuronal infection.

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Vesicular stomatitis virus: Immune recognition, responsiveness, and pathogenesis of infection in mice

Reiss

Aoki

1994

Reviews in Medical Virology

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Lymphokine Expression Profile of Resting and Stimulated CD4+ CTL Clones Specific for the Glycoprotein of Vesicular Stomatitis Virus

Cited by 5 publications

References 0 publications

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4⁺Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4⁺Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Antiviral protection by vesicular stomatitis virus-specific antibodies in alpha/beta interferon receptor-deficient mice

Vesicular stomatitis virus: Immune recognition, responsiveness, and pathogenesis of infection in mice

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Lymphokine Expression Profile of Resting and Stimulated CD4+ CTL Clones Specific for the Glycoprotein of Vesicular Stomatitis Virus

Cited by 5 publications

References 0 publications

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4+Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4+Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Antiviral protection by vesicular stomatitis virus-specific antibodies in alpha/beta interferon receptor-deficient mice

Vesicular stomatitis virus: Immune recognition, responsiveness, and pathogenesis of infection in mice

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Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4⁺Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4⁺Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge