Accession Number : ADA582079


Title :   Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG


Descriptive Note : Journal article


Corporate Author : WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY


Personal Author(s) : Tomaras, Georgia D ; Ferrari, Guido ; Shen, Xiaoying ; Alam, S M ; Liao, Hua-Xin ; Pollara, Justin ; Bonsignori, Mattia ; Moody, M A ; Fong, Youyi ; Chen, Xi


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a582079.pdf


Report Date : 28 May 2013


Pagination or Media Count : 9


Abstract : Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses directly correlated with risk. In the secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate of risk, but only in the presence of low plasma IgA Env-specific antibodies. Thus, we investigated the hypothesis that IgA could attenuate the protective effect of IgG responses through competition for the same Env binding sites. We report that Env-specific plasma IgA/IgG ratios are higher in infected than in uninfected vaccine recipients in RV144. Moreover, Env-specific IgA antibodies from RV144 vaccines blocked the binding of ADCC-mediating mAb to HIV-1 Env glycoprotein 120 (gp120). An Env-specific monomeric IgA mAb isolated from an RV144 vaccinee also inhibited the ability of natural killer cells to kill HIV-1 infected CD4+ T cells coated with RV144-induced IgG antibodies. We show that monomeric Env-specific IgA, as part of postvaccination polyclonal antibody response, may modulate vaccine-induced immunity by diminishing ADCC effector function.


Descriptors :   *BLOOD PLASMA , *HUMAN IMMUNODEFICIENCY VIRUSES , *IMMUNOGLOBULINS , *VACCINES , ANTIBODIES , CASE STUDIES , PROTEINS


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE