Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.

• Type of Material: Article
• Authors: Venkateswarlu Chamcha, Emory University; Sunil Kannanganat, Emory University; Sailaja Gangadhara, Emory University; Rafiq Nabi, Louisiana State University; Pamela A. Kozlowski, Louisiana State University; David C. Montefiori, Duke University; Celia C. LaBranche, Duke University; Jens Wrammert, Emory University; Brandon F. Keele, Frederick National Laboratory for Cancer Research; Harikrishnan Balachandran, Beth Israel Deaconess Medical Center; Sujata Sahu, Beth Israel Deaconess Medical Center; Michelle Lifton, Beth Israel Deaconess Medical Center; Sampa Santra, Beth Israel Deaconess Medical Center; Rahul Basu, Geovax Inc; Bernard Moss, National Institute of Allergy and Infectious Diseases; Harriet Robinson, Emory University; Rama Amara, Emory University
• Language: English
• Date: 2016-01
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/ofid/ofw034
• Title of Journal or Parent Work: Open Forum Infectious Diseases
• ISSN: 2328-8957
• Volume: 3
• Issue: 1
• Start Page: ofw034
• End Page: ofw034
• Grant/Funding Information: This trial, P165, was funded by the Simian Vaccine Evaluation Unit of the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID); the Primate Central Immunology Laboratory (Contract no. HHSN272201100016C; to D. C. M.); an Integrated Preclinical/Clinical AIDS Vaccine Development Grant (5U19AI074073; to H. L. R.); the Consortia for AIDS Vaccine Research in Nonhuman Primates Grant (U19AI096187; to R. R. A.); and funded in part with federal funds from the National Cancer Institute, National Institutes of Health (under Contract No. HHSN261200800001E) and the Division of Intramural Research, NIAID.
• Keywords: SIV; DNA/MVA vaccine; age-dependent protection; HIV vaccine; antibody
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Immunology

Abstract

Background: In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods: The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results: Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions: The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques.