title: Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.
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.
authors.affiliation: Yerkes National Primate Research Center, Emory University , Atlanta, Georgia.
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Chamcha
authors.affiliation: Yerkes National Primate Research Center, Emory University , Atlanta, Georgia.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kannanganat
authors.affiliation: Yerkes National Primate Research Center, Emory University , Atlanta, Georgia.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Gangadhara
authors.affiliation: Department of Microbiology , Immunology and Parasitology, Louisiana State University Health Sciences Center , New Orleans.
authors.forename: Rafiq
authors.initials: R
authors.lastname: Nabi
authors.affiliation: Department of Microbiology , Immunology and Parasitology, Louisiana State University Health Sciences Center , New Orleans.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Kozlowski
authors.affiliation: Duke University Medical Center , Durham, North Carolina.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke University Medical Center , Durham, North Carolina.
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.affiliation: Department of Pediatrics , Emory University School of Medicine , Atlanta, Georgia.
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc. , Frederick National Laboratory for Cancer Research , Maryland.
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.affiliation: Harvard Medical School, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Balachandran
authors.affiliation: Harvard Medical School, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors.forename: Sujata
authors.initials: S
authors.lastname: Sahu
authors.affiliation: Harvard Medical School, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lifton
authors.affiliation: Harvard Medical School, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.affiliation: Geovax Inc , Smyrna, Georgia.
authors.forename: Rahul
authors.initials: R
authors.lastname: Basu
authors.affiliation: Laboratory of Viral Diseases , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.affiliation: Geovax Inc , Smyrna, Georgia.
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
authors.affiliation: Yerkes National Primate Research Center, Emory University , Atlanta, Georgia.
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
keywords: DNA/MVA vaccine; HIV vaccine; SIV; age-dependent protection; antibody