Active Mycobacterium tuberculosis Co-Infection Associates With Higher HIV-1-Specific Antibody Responses

Abstract

Mycobacterium tuberculosis (TB) can enhance immune responses against unrelated pathogens. Here, we show that HIV-1 neutralizing antibodies (nAb), but not antibody-dependent cellular cytotoxicity (ADCC) are broader and more potent in individuals with TB co-infection. In the TB co-infected people (HIV-1/TB) but not those without TB (HIV-1 only), nAbs and ADCC are strongly correlated. HIV-1 envelope sequence motifs associated with neutralization are differentially present in the HIV-1/TB and HIV-1 only group, implying unique selection pressures. The usual factors associated with enhanced HIV-1 nAbs, namely higher plasma virus levels, lower absolute CD4 counts, and increased envelope genetic diversity, are not different in the two groups. TB co-infection associates with the enhancement of HIV-1 but not all antibodies. Specific mediators important for B cell development are elevated in the HIV-1/TB individuals and associate with higher nAbs. Pathways perturbed by TB co-infection should be investigated and leveraged to induce optimal HIV-1 antibody responses.

Keywords: HIV-1/TB co-infection, heterologous immunity, neutralizing antibody, antibody-dependent cellular cytotoxicity, envelope sequence motifs, and B cell development mediators