Robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus DNA prime and live virus vector boost vaccination of lactating rhesus monkeys

J Immunol. 2010 Dec 1;185(11):7097-106. doi: 10.4049/jimmunol.1002751. Epub 2010 Nov 1.

Abstract

Breast milk transmission of HIV remains an important mode of infant HIV acquisition. Enhancement of mucosal HIV-specific immune responses in milk of HIV-infected mothers through vaccination may reduce milk virus load or protect against virus transmission in the infant gastrointestinal tract. However, the ability of HIV/SIV strategies to induce virus-specific immune responses in milk has not been studied. In this study, five uninfected, hormone-induced lactating, Mamu A*01(+) female rhesus monkey were systemically primed and boosted with rDNA and the attenuated poxvirus vector, NYVAC, containing the SIVmac239 gag-pol and envelope genes. The monkeys were boosted a second time with a recombinant Adenovirus serotype 5 vector containing matching immunogens. The vaccine-elicited immunodominant epitope-specific CD8(+) T lymphocyte response in milk was of similar or greater magnitude than that in blood and the vaginal tract but higher than that in the colon. Furthermore, the vaccine-elicited SIV Gag-specific CD4(+) and CD8(+) T lymphocyte polyfunctional cytokine responses were more robust in milk than in blood after each virus vector boost. Finally, SIV envelope-specific IgG responses were detected in milk of all monkeys after vaccination, whereas an SIV envelope-specific IgA response was only detected in one vaccinated monkey. Importantly, only limited and transient increases in the proportion of activated or CCR5-expressing CD4(+) T lymphocytes in milk occurred after vaccination. Therefore, systemic DNA prime and virus vector boost of lactating rhesus monkeys elicits potent virus-specific cellular and humoral immune responses in milk and may warrant further investigation as a strategy to impede breast milk transmission of HIV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • DNA, Recombinant / administration & dosage
  • DNA, Recombinant / immunology
  • DNA, Viral / administration & dosage
  • DNA, Viral / genetics
  • DNA, Viral / immunology*
  • Female
  • Gene Products, env / administration & dosage
  • Gene Products, env / genetics
  • Gene Products, env / immunology
  • Gene Products, gag / administration & dosage
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology
  • Gene Products, pol / administration & dosage
  • Gene Products, pol / genetics
  • Gene Products, pol / immunology
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / immunology*
  • Immunity, Cellular*
  • Immunization, Secondary / methods*
  • Lactation / genetics
  • Lactation / immunology*
  • Macaca mulatta
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / immunology*
  • Mammary Glands, Animal / metabolism
  • Poxviridae / genetics
  • Poxviridae / immunology
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control
  • Simian Acquired Immunodeficiency Syndrome / transmission
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology

Substances

  • Antibodies, Viral
  • DNA, Recombinant
  • DNA, Viral
  • Gene Products, env
  • Gene Products, gag
  • Gene Products, pol
  • SAIDS Vaccines
  • Vaccines, Attenuated