Antibody to the gp120 V1/V2 loops and CD4+ and CD8+ T cell responses in protection from SIVmac251 vaginal acquisition and persistent viremia.
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.
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892;
Shari N
SN
Gordon
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892;
Melvin N
MN
Doster
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20982;
Rhonda C
RC
Kines
AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
Brandon F
BF
Keele
Vaccine Branch, National Cancer Institute, Bethesda, MD 20892;
Egidio
E
Brocca-Cofano
Division of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
Yongjun
Y
Guan
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892;
Poonam
P
Pegu
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892;
Namal P M
NP
Liyanage
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892;
Monica
M
Vaccari
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20982;
Nicolas
N
Cuburu
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20982;
Christopher B
CB
Buck
Department of Surgery, Duke University Medical Center, Durham, NC 27710;
Guido
G
Ferrari
Department of Surgery, Duke University Medical Center, Durham, NC 27710;
David
D
Montefiori
AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
Michael
M
Piatak
AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
Jeffrey D
JD
Lifson
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892;
Anastasia M
AM
Xenophontos
Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892; and.
David
D
Venzon
Vaccine Branch, National Cancer Institute, Bethesda, MD 20892;
Marjorie
M
Robert-Guroff
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Barney S
BS
Graham
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20982;
Douglas R
DR
Lowy
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20982;
John T
JT
Schiller
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892; franchig@mail.nih.gov.
Genoveffa
G
Franchini
D052685:Alphapapillomavirus / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D010446:Peptide Fragments / Q000276:immunology*; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology* / Q000821:virology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology* / Q000517:prevention & control / Q000821:virology
D000914:Antibodies, Viral; D010446:Peptide Fragments; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins