title: Impact of antibody quality and anamnestic response on viremia control post-challenge in a combined Tat/Env vaccine regimen in rhesus macaques.
abstract: Previously, priming rhesus macaques with Adenovirus type 5 host range mutant-recombinants encoding Tat and Env and boosting with Tat and Env protein in MPL-SE controlled chronic viremia by 4 logs following homologous intravenous SHIV89.6P challenge. Here we evaluated Tat, Env, and Tat/Env regimens for immunogenicity and protective efficacy using clade C Env, alum adjuvant, and a heterologous intrarectal SHIV1157ipd3N4 challenge. Despite induction of strong cellular and humoral immunity, Tat/Env group T and B-cell memory responses were not significantly enhanced over Tat- or Env-only groups. Lack of viremia control post-challenge was attributed to lower avidity Env antibodies and no anamnestic ADCC response or SHIV1157ipd3N4 neutralizing antibody development post-challenge. Poor biologic activity of the Tat immunogen may have impaired Tat immunity. In the absence of sterilizing immunity, strong anamnestic responses to heterologous virus can help control viremia. Both antibody breadth and optimal adjuvanticity are needed to elicit high-quality antibody for protective efficacy.
authors.affiliation: Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Seraphin
authors.initials: S
authors.lastname: Kuate
authors.forename: Stanley
authors.initials: S
authors.lastname: Aladi
authors.forename: Diego A
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Irene
authors.initials: I
authors.lastname: Kalisz
authors.forename: V S
authors.initials: VS
authors.lastname: Kalyanaraman
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: Janet
authors.initials: J
authors.lastname: DiPasquale
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
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: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D015686:Gene Products, env / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014766:Viremia / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D015696:Gene Products, tat; D018449:SAIDS Vaccines; C041524:aluminum sulfate