An Effective AIDS Vaccine Based on Live Attenuated Vesicular Stomatitis Virus Recombinants

• Published in: Cell Vol. 106; no. 5; pp. 539 - 549
• Main Authors: Rose, Nina F., Marx, Preston A., Luckay, Amara, Nixon, Douglas F., Moretto, Walter J., Donahoe, Sean M., Montefiori, David, Roberts, Anjeanette, Buonocore, Linda, Rose, John K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07-09-2001
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - prevention & control; Acquired Immunodeficiency Syndrome - virology; AIDS Vaccines - administration & dosage; AIDS Vaccines - genetics; AIDS Vaccines - immunology; Animals; CD4 antigen; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; env gene; Enzyme-Linked Immunosorbent Assay; gag gene; Gene Products, env - genetics; Gene Products, env - immunology; Gene Products, gag - genetics; Gene Products, gag - immunology; HIV - immunology; HIV - physiology; HIV Antibodies - biosynthesis; Human immunodeficiency virus; Humans; Immunization, Secondary; Macaca mulatta; Mice; Neutralization Tests; Pilot Projects; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - 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; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - physiology; Simian/human immunodeficiency virus; T-Lymphocytes, Cytotoxic - immunology; Time Factors; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccines, Synthetic - immunology; Vesicular stomatitis Indiana virus - genetics; Vesicular stomatitis Indiana virus - immunology; Vesicular stomatitis virus; Viral Load; Virus Shedding
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(01)00482-2

We developed an AIDS vaccine based on attenuated VSV vectors expressing
env and
gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4
+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.