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.
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.
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Andrew B
AB
Wilks
Elizabeth C
EC
Christian
Michael S
MS
Seaman
Piya
P
Sircar
Angela
A
Carville
Carmen E
CE
Gomez
Mariano
M
Esteban
Giuseppe
G
Pantaleo
Dan H
DH
Barouch
Norman L
NL
Letvin
Sallie R
SR
Permar
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000276:immunology; D004279:DNA, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015684:Gene Products, pol / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular; D007117:Immunization, Secondary / Q000379:methods*; D007774:Lactation / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D011212:Poxviridae / Q000235:genetics / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D004274:DNA, Recombinant; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated