Challenges for vaccination against sexually-transmitted diseases: induction and long-term maintenance of mucosal immune responses in the female genital tract

Rosenthal, Kenneth L.; Gallichan, W. Scott

doi:10.1006/smim.1997.0086

Cited by 55 publications

(35 citation statements)

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“…Intranasal immunization has been proven by numerous reports to be particularly effective in inducing immune responses in the female genital tract (14,15,25,44,46). Studies done in macaques with attenuated vaccinia virus that express Env and Gag proteins of SIV or recombinant live attenuated poliovirus expressing the SIV proteins p17 gag and gp41 env confirmed these findings regarding antibody responses (12,33).…”

Section: Discussionmentioning

confidence: 85%

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Stevceva

Álvarez

Lackner

et al. 2002

J Virol

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As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A‫10ء‬ molecule to assess the capacity of the highly attenuated poxvirus NYVAC/simian immunodeficiency virus (SIV) SIV gpe vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIV mac251 by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NYVAC/SIV gpe and the anamnestic response to SIV mac251 at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIV mac Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigenspecific CD8؉ T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIV mac251 challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8 ؉ T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes.

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Section: Discussionmentioning

confidence: 85%

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Stevceva

Álvarez

Lackner

et al. 2002

J Virol

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“…Intranasal (IN) immunization, on the other hand, has been more promising in terms of eliciting genital-tract antigen-specific IgA and IgG in mice (18,21,47), primates (42), and humans (3,38). In addition, the genital-tract antibodies generated as a function of IN immunization have been demonstrated to be long lasting in mice (37,47) Cholera toxin B (Ctb), the nonenzymatic, nontoxic component of cholera toxin, has been studied extensively for its ability to augment antibody responses to coadministered and physically conjugated antigens following intranasal application (21,23,24,48,49). In this study, we evaluated the immunogenicity of IN administered recombinant TbpA and TbpB, alone and in combination with recombinant Ctb.…”

mentioning

confidence: 99%

Intranasal Administration of RecombinantNeisseria gonorrhoeaeTransferrin Binding Proteins A and B Conjugated to the Cholera Toxin B Subunit Induces Systemic and Vaginal Antibodies in Mice

2005

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“…These shortcomings are likely due to deficiencies in the induction of appropriate mucosal associated immune responses (1)(2)(3). A crucial role for local mucosal immune responses is illustrated by the observation that HIV-exposed uninfected sex workers have HIV-1-specific neutralizing IgA in genital tract secretions (4 -6) and HIV-specific CD8 ϩ T cells in the cervix (7).…”

mentioning

confidence: 99%

“…The administration of Ag to mucosal surfaces is possibly the best method of inducing mucosal immune responses at distant as well as local sites (1)(2)(3). However, one of the major impediments to implementation of mucosal vaccines has been the lack of effective yet safe mucosal adjuvants.…”

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confidence: 99%

Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract

Gallichan¹,

Woolstencroft²,

Guarasci

et al. 2001

The Journal of Immunology

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199

134

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Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HSV and HIV, will likely be dependent on the induction of potent long-lasting mucosal immune responses in the genital tract. Recently, synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs were shown to serve as potent adjuvants for the induction of mucosal immune responses. Here, we show that intranasal immunization with CpG ODN, plus recombinant glycoprotein B (rgB) of HSV-1, results in significantly elevated levels of specific anti-gB IgA Abs in vaginal washes that remained high throughout the estrous cycle. Additionally, dramatically elevated numbers of specific IgA Ab-secreting cells were present and persisted in the genital tract in response to intravaginal (IVAG) HSV-2 challenge. HSV-2-specific CTL were observed at moderate levels in the spleens of CpG or non-CpG ODN-immunized mice. In contrast, strong CTL responses were observed locally in the genital tissues of both groups following IVAG HSV-2 challenge. Interestingly, mice immunized intranasally with rgB plus CpG ODN, but not non-CpG ODN, were significantly protected following IVAG HSV-2 challenge. Measurement of virus in protected CpG-immunized mice revealed a log lower level of replication within the first few days after infection. In conclusion, these results indicate that intranasal immunization with CpG ODN plus protein mediates immunity in the female genital tract capable of protecting against a sexually transmitted pathogen.

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Challenges for vaccination against sexually-transmitted diseases: induction and long-term maintenance of mucosal immune responses in the female genital tract

Cited by 55 publications

References 0 publications

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Intranasal Administration of RecombinantNeisseria gonorrhoeaeTransferrin Binding Proteins A and B Conjugated to the Cholera Toxin B Subunit Induces Systemic and Vaginal Antibodies in Mice

Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract

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Challenges for vaccination against sexually-transmitted diseases: induction and long-term maintenance of mucosal immune responses in the female genital tract

Cited by 55 publications

References 0 publications

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpeRecombinant Vaccine Result in Gag-Specific CD8+T-Cell Responses in Mucosal Tissues of Macaques

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpeRecombinant Vaccine Result in Gag-Specific CD8+T-Cell Responses in Mucosal Tissues of Macaques

Intranasal Administration of RecombinantNeisseria gonorrhoeaeTransferrin Binding Proteins A and B Conjugated to the Cholera Toxin B Subunit Induces Systemic and Vaginal Antibodies in Mice

Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract

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Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques