title: HIV-1-Specific Antibody Response and Function after DNA Prime and Recombinant Adenovirus 5 Boost HIV Vaccine in HIV-Infected Subjects.
abstract: Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir.
authors: Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
authors: Johannes S
authors: JS
authors: Gach
authors: Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
authors: Andrea
authors: A
authors: Gorlani
authors: Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
authors: Emmanuel Y
authors: EY
authors: Dotsey
authors: Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
authors: Juan C
authors: JC
authors: Becerra
authors: Department of Medicine, Feinberg School of Medicine, Division of Infectious Diseases, Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
authors: Chase T M
authors: CT
authors: Anderson
authors: Department of Medicine, Feinberg School of Medicine, Division of Infectious Diseases, Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
authors: Baiba
authors: B
authors: Berzins
authors: Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
authors: Philip L
authors: PL
authors: Felgner
authors: Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
authors: Donald N
authors: DN
authors: Forthal
authors: HIV/AIDS Division, San Francisco General Hospital and University of California San Francisco, San Francisco, California, United States of America.
authors: Steven G
authors: SG
authors: Deeks
authors: Division of Infectious Diseases, Weill Cornell Medical College, New York, United States of America.
authors: Timothy J
authors: TJ
authors: Wilkin
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors: Joseph P
authors: JP
authors: Casazza
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors: Richard A
authors: RA
authors: Koup
authors: Department of Infectious Diseases, Pitié-Salpêtrière Hospital, Paris, France.
authors: Christine
authors: C
authors: Katlama
authors: Department of Immunology, Pitié-Salpêtrière Hospital, Paris, France.
authors: Brigitte
authors: B
authors: Autran
authors: Department of Medicine, Feinberg School of Medicine, Division of Infectious Diseases, Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
authors: Robert L
authors: RL
authors: Murphy
authors: Department of Medicine, Feinberg School of Medicine, Division of Infectious Diseases, Center for Global Health, Northwestern University, Chicago, Illinois, United States of America.
authors: Chad J
authors: CJ
authors: Achenbach
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D019444:Vaccines, DNA