title: Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001.
abstract: HIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design.
  
  
  OBJECTIVE
  The roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Costa
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Pollara
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Regina Whitney
authors.initials: RW
authors.lastname: Edwards
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York, USA.
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA shan.lu@umassmed.edu.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004247:DNA / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D011961:Receptors, Fc / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology; D014838:Volunteers; D054299:env Gene Products, Human Immunodeficiency Virus / Q000493:pharmacokinetics*
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011961:Receptors, Fc; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C050598:vaccin; D004247:DNA