Humoral Antibody Responses to HIV Viral Proteins and to CD4 Among HIV Controllers, Rapid and Typical Progressors in an HIV-Positive Patient Cohort

Abstract

The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV+ cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV+ subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC. All of the HIV+ patient samples were positive for antibodies to HIV gp120 and p24 and 80% showed evidence of hypergammaglobulinemia. Approximately 10% of cohort members were positive for antibodies to CD4, but we noted no significant correlation relevant to DP. There were statistically significant differences between the groups concerning the level of humoral response to gp120 and Gag. However, we observed no distinction in ability of anti-gp120 antibodies purified from each group to neutralize infection. In addition, there was a statistically significant difference in ADCC, with elite controllers exhibiting significantly lower levels of ADCC than the other five groups. We detected IgA anti-gp120 antibodies, but did not correlate their presence with either DP or ADCC levels. The results are consistent with the interpretation that the humoral antibody response to the antigens assessed here represents a signature of the level of viremia but does not correlate with clinical status of HIV infection.

Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy

“…As EC better maintain HIV-specific CD4 T cells than HAART recipients, they may develop higher quality HIV-specific IgA responses, including broader IgA responses to HIV antigens and higher avidity IgA antibodies. No information regarding mucosal IgA responses is available for EC, and studies of HIV-specific IgA in serum of EC are limited [ 8 , 35 , 36 ] and somewhat conflicting. For example, in one study, levels of anti-gp120 serum IgA were not found to differ in EC and progressors [ 35 ].…”

“…No information regarding mucosal IgA responses is available for EC, and studies of HIV-specific IgA in serum of EC are limited [ 8 , 35 , 36 ] and somewhat conflicting. For example, in one study, levels of anti-gp120 serum IgA were not found to differ in EC and progressors [ 35 ]. However, others have reported that EC better maintain levels of gp120-specific serum IgA antibodies than acutely- or chronically-infected individuals not on HAART [ 36 ].…”

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“…In 2016, an estimated 53% of HIV-infected individuals resided in sub-Saharan Africa [1]. Heterogeneity in phenotypic responses to HIV infection suggest different rates of progression to AIDS [2][3][4][5]. Although the vast majority of HIV-infected individuals are categorized as chronic progressors (CPs) and, in absence of anti-retroviral therapy (ART), will progress to AIDS approximately a decade after seroconversion [6], two controller phenotypic manifestations of HIV infection and progression are described in people in the absence of ART.…”