Antibody to the gp120 V1/V2 loops and CD4+ and CD8+ T cell responses in protection from SIVmac251 vaginal acquisition and persistent viremia

J Immunol. 2014 Dec 15;193(12):6172-83. doi: 10.4049/jimmunol.1401504. Epub 2014 Nov 14.

Abstract

The human papillomavirus pseudovirions (HPV-PsVs) approach is an effective gene-delivery system that can prime or boost an immune response in the vaginal tract of nonhuman primates and mice. Intravaginal vaccination with HPV-PsVs expressing SIV genes, combined with an i.m. gp120 protein injection, induced humoral and cellular SIV-specific responses in macaques. Priming systemic immune responses with i.m. immunization with ALVAC-SIV vaccines, followed by intravaginal HPV-PsV-SIV/gp120 boosting, expanded and/or recruited T cells in the female genital tract. Using a stringent repeated low-dose intravaginal challenge with the highly pathogenic SIVmac251, we show that although these regimens did not demonstrate significant protection from virus acquisition, they provided control of viremia in a number of animals. High-avidity Ab responses to the envelope gp120 V1/V2 region correlated with delayed SIVmac251 acquisition, whereas virus levels in mucosal tissues were inversely correlated with antienvelope CD4(+) T cell responses. CD8(+) T cell depletion in animals with controlled viremia caused an increase in tissue virus load in some animals, suggesting a role for CD8(+) T cells in virus control. This study highlights the importance of CD8(+) cells and antienvelope CD4(+) T cells in curtailing virus replication and antienvelope V1/V2 Abs in preventing SIVmac251 acquisition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alphapapillomavirus / genetics
  • Animals
  • Antibodies, Viral / immunology*
  • Antibody Specificity / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Female
  • Genetic Vectors / genetics
  • Lymphocyte Depletion
  • Macaca mulatta
  • Molecular Sequence Data
  • Mucous Membrane / immunology
  • Mucous Membrane / virology
  • Peptide Fragments / immunology*
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / virology
  • Vaccination
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vagina / immunology*
  • Vagina / virology
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viremia / immunology*
  • Viremia / prevention & control
  • Viremia / virology

Substances

  • Antibodies, Viral
  • Peptide Fragments
  • SAIDS Vaccines
  • Vaccines, DNA
  • Viral Envelope Proteins

Associated data

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