BACKGROUND: The safety and immunogenicity of the MRK adenovirus type5 human immunodeficiency virus type 1clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5-vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial. METHODS:Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5 human immunodeficiency virus type 1 vaccine containing from 3 x 10(6) to 1 x 10(11) viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-gamma enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose. RESULTS: Of 259 randomized individuals, 257 (99%) received > or = 1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of > or = 3 x 10(9) viral particles elicited positive enzyme-linked immunosorbent spot responses to > or = 1 vaccine component in > 60% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzyme-linked immunosorbent spot responses at all doses except the 3 x 10(10) viral particle dose. CONCLUSIONS: The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy.
RCT Entities:
BACKGROUND: The safety and immunogenicity of the MRK adenovirus type 5human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5-vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial. METHODS: Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5human immunodeficiency virus type 1 vaccine containing from 3 x 10(6) to 1 x 10(11) viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-gamma enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose. RESULTS: Of 259 randomized individuals, 257 (99%) received > or = 1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of > or = 3 x 10(9) viral particles elicited positive enzyme-linked immunosorbent spot responses to > or = 1 vaccine component in > 60% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzyme-linked immunosorbent spot responses at all doses except the 3 x 10(10) viral particle dose. CONCLUSIONS: The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy.
Authors: Jacques Fellay; Nicole Frahm; Kevin V Shianna; Elizabeth T Cirulli; Danilo R Casimiro; Michael N Robertson; Barton F Haynes; Daniel E Geraghty; M Juliana McElrath; David B Goldstein Journal: J Infect Dis Date: 2011-01-28 Impact factor: 5.226
Authors: Lauren A Hirao; Ling Wu; Abhishek Satishchandran; Amir S Khan; Ruxandra Draghia-Akli; Adam C Finnefrock; Andrew J Bett; Michael R Betts; Danilo R Casimiro; Niranjan Y Sardesai; J Joseph Kim; John W Shiver; David B Weiner Journal: Mol Ther Date: 2010-06-15 Impact factor: 11.454
Authors: John B Schell; Nina F Rose; Kapil Bahl; Kathryn Diller; Linda Buonocore; Meredith Hunter; Preston A Marx; Ratish Gambhira; Haili Tang; David C Montefiori; Welkin E Johnson; John K Rose Journal: J Virol Date: 2011-04-13 Impact factor: 5.103
Authors: Clayton Harro; Xiao Sun; Jon E Stek; Randi Y Leavitt; Devan V Mehrotra; Fubao Wang; Andrew J Bett; Danilo R Casimiro; John W Shiver; Mark J DiNubile; Erin Quirk Journal: Clin Vaccine Immunol Date: 2009-07-15