title: Effective induction of simian immunodeficiency virus-specific systemic and mucosal immune responses in primates by vaccination with proviral DNA producing intact but noninfectious virions.
abstract: We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong virus-specific mucosal immune responses in primates. The levels of immunoglobulin A (IgA) detected in rectal secretions of macaques that received the DNA vaccine intradermally and at the rectal mucosa were the most striking of all measured immune responses and were higher than usually achieved through natural infection. However, cytotoxic T lymphocyte responses were generally low and sporadically present in different animals. Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected. Our results suggest that high levels of IgA alone are not sufficient to prevent the establishment of chronic infection, although mucosal IgA responses may have a role in reducing the infectivity of the initial viral inoculum.
authors.affiliation: Department of Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Wang
authors.forename: P A
authors.initials: PA
authors.lastname: Kozlowski
authors.forename: G
authors.initials: G
authors.lastname: Schmelz
authors.forename: K
authors.initials: K
authors.lastname: Manson
authors.forename: M S
authors.initials: MS
authors.lastname: Wyand
authors.forename: R
authors.initials: R
authors.lastname: Glickman
authors.forename: D
authors.initials: D
authors.lastname: Montefiori
authors.forename: J D
authors.initials: JD
authors.lastname: Lifson
authors.forename: R P
authors.initials: RP
authors.lastname: Johnson
authors.forename: M R
authors.initials: MR
authors.lastname: Neutra
authors.forename: A
authors.initials: A
authors.lastname: Aldovini
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D008253:Macaca mulatta; D011533:Proviruses / Q000235:genetics; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000502:physiology
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D007070:Immunoglobulin A; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA