Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine. (11th February 2016)

• Record Type: Journal Article
• Authors: Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja; Nabi, Rafiq; Kozlowski, Pamela A.; Montefiori, David C.; LaBranche, Celia C.; Wrammert, Jens; Keele, Brandon F.; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Santra, Sampa; Basu, Rahul; Moss, Bernard; Robinson, Harriet L.; Amara, Rama Rao
• Is Part Of: Open forum infectious diseases. Volume 3:Number 1(2016)
• Publication Date: 2016-02-11
• Subjects: age-dependent protection -- antibody -- DNA/MVA vaccine -- HIV vaccine -- SIV; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofw034
• Languages: English
• ISSNs: 2328-8957

Abstract

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.