Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization

ADDTIONAL ARTICLES Lymphoid activation: a confounding factor in AIDS vaccine development? Steering a Course to an AIDS Vaccine AIDS Vaccination Studies Using FIV Model: Failure To Protect and Possible Enhancement of Challenge Infection Tat-Vaccinated Macaques Do Not Control Simian Immunodeficiency Virus SIVmac239 Replication Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes Control of a Mucosal Challenge and Prevention of AIDS in Rhesus Macaques Induction of SIV-specific immune responses in primates by vaccination with proviral DNA Pathogenic S/HIV SHIVKU inoculated into immunized macaques Cytokine-augmented DNA vaccination Vaccine protection against SIV by recombinant strains of Herpes Simplex Virus Genetically modified anthrax lethal toxin in the treatment of AIDS Augmentation of immune responses to HIV-1 and SIV DNA vaccines Recombination of live-attenuated immunodeficiency virus vaccine with challenge virus to a more virulent strain Cytokine cDNAs as DNA vaccine adjuvants Human neutralizing monoclonal antibodies protect against mucosal simian-human immunodeficiency virus infection Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus Analysis of the HIV-1 nef gene in five intravenous drug users with long-term nonprogressive HIV-1 infection in Italy Pathogenic Conversion of Live Attenuated Simian Immunodeficiency Virus Vaccines Is Associated with Expression of Truncated Nef Allo-immunization elicits HIV suppressor factors and resistance to HIV infection in women Infection with attenuated HIV and the progression of AIDS Use of Tat protein in a vaccine SIV highly attenuated vaccine protectes against vaginal challenge Viral diversity in macaques immunized with live-attenuated SIV Live attenuated viral vaccine causes AIDS in infant and adult macaques Fusion-competent vaccines: A mouse model Risk in using live/attenuated HIV-1 vaccine strains Protective immunity against HIV? Mucosal immunity against HIV-1 Recombinant gp120 subunit vaccines Infection with HIV-IIIB/neutralizing antibodies Escape mutants after immunization SIV attenuated mutants Passive immunization/hu-PBL-SCID protection against HIV infection Vaccine for HIV/antibody strategy Targeting HIV proteins to MHC I processing pathway/vaccine development Laboratory isolates and sensitivity to neutralization Live attenuated SIV vaccine/CTL response Mucosal immunity against SIV infection SIV attenuated vaccines and protective immunity Live-attenuated SIV vaccine SIV live-attenuated vaccines: stimulation results in no reactivation of virus Use of attenuated chimeric virus as a vaccine Recombinant adenovirus expressing gag induces an immune response Adenovirus-SIV recombinant vaccine Mechanism of protection via attenuated SIV Infection with attenuated SIV/resistance to superinfection HIV envelope DNA/protein vaccination Enhanced immunogenicity of HIV-1 vaccine

Michael D. Lubeck¹, Robert Natuk¹, Maria Myagkikh², Narender Kalyan¹, Kristine Aldrich², Faruk Sinangil³, Shabnam Alipanah², Shri C.S. Murthy¹, Pranab K. Chanda¹, Stephen M. Nigida, Jr.⁴, Phillip D. Markham⁵, Susan Zolla-Pazner⁶, Kathy Steimer³, Mark Wade¹, Marvin S. Reitz, Jr.², Larry O. Arthur⁴, Satoshi Mizutani¹, Alan Davis¹, Paul P. Hung¹, Robert C. Gallo², Jorg Eichberg¹ & Marjorie Robert-Guroff^2
1Wyeth-Ayerst Research, 145 King of Prussia Road, Radnor, PA 19087, USA, ²Laboratory of Tumor Cell Biology, National Cancer Institute, Building 37, Room 6B03, National Institutes of Health, Bethesda, MD 20892-4255, USA, ³Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608-2916, USA, ⁴Program Resources, Inc., Frederick Cancer Research and Development Center, National Cancer Institute, P.O. Box B, Frederick, MD 21702, USA, ⁵Advanced BioScience Laboratories, 5510 Nicholson Lane, Kensington, MD 20895-1078, USA, ⁶Veterans Affairs Medical Centers, New York, NY 10010, USA, M.D.L. present address: Wyeth-Lederle Vaccines & Pediatrics, P.O. Box 304, Marietta, PA 17547, USA, R.N., N.K., S.M. present address: Wyeth-Lederle Vaccines, 401 North Middleton Road, Pearl River, NY 10965 USA, A.D. present address: Institute for Gene Therapy, University of Pennsylvania, 601 Maloney Building, 36th & Spruce Streets, Philadelphia, PA 19104, USA, P.P.H. present address: 506 Ramblewood, Bryn Mawr, PA 19010, USA, M.S.R., R.C.G. present address: Institute of Human Virology, Medical Biotechnology Center, University of Maryland at Baltimore, 725 West Lombard Street, Baltimore, MD 21201, USA, J.E. present address: Dutch Primate Centre, Biomedical Primate Research Centre, Lange Kleiweg 151, 2280HV Rijswijk, the Netherlands

A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1_MN gp160 recombinants followed by boosting with HIV-1_SF2 gp120 was evaluated in chimpanzees. Long-lasting protection, requiring only three immunizations, was achieved against a low-dose challenge with the SF2 strain of HIV-1 and a subsequent high-dose SF2 challenge administered 1 year later without an intervening boost. Notably, neutralizing antibody responses against both clinical and laboratory isolates developed in three chimpanzees and persisted until the time of high-dose challenge. The possibility that cytotoxic T-lymphocytes contribute to low-dose protection of a chimpanzee lacking neutralizing antibodies is suggested. Our results validate the live vector priming/subunit booster approach and should stimulate interest in assessing this combination vaccine approach in humans.