title: Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus.
abstract: The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value<0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value <0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.
authors.affiliation: New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, P.O. Box 9102, Southborough, MA 01772-9102, USA. amitinder_kaur@hms.harvard.edu
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
authors.forename: Hannah B
authors.initials: HB
authors.lastname: Sanford
authors.forename: Deirdre
authors.initials: D
authors.lastname: Garry
authors.forename: Sabine
authors.initials: S
authors.lastname: Lang
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Klumpp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D005822:Genetic Vectors; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA