title: Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies.
abstract: A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1(MN)env/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIV(SF162) gp140deltaV2. The immunogenicities of replicating and nonreplicating Ad/HIV-1(MN)env/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1(SF162) gp140deltaV2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful.
authors.affiliation: Vaccine Branch, NIH, NCI, 41 Medlars Dr., Bldg. 41, Bethesda, MD 20892-5065, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Liqun Rejean
authors.initials: LR
authors.lastname: Wang
authors.forename: Victor Raúl
authors.initials: VR
authors.lastname: Gómez-Román
authors.forename: Alberta
authors.initials: A
authors.lastname: Davis-Warren
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: V S
authors.initials: VS
authors.lastname: Kalyanaraman
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Elaine
authors.initials: E
authors.lastname: Kan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rowell
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Murthy
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood*; D007114:Immunization; D008213:Lymphocyte Activation; D002679:Pan troglodytes; D012107:Research Design; D014614:Vaccines, Synthetic / Q000276:immunology*; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D014614:Vaccines, Synthetic