Neutralizing Antibodies in Mucosal Secretions: IgG or IgA?

Abstract

The mucosal immune response to HIV weighs in heavily on the battle against it, as the majority of infections occur via the mucosal route. The antibody response in the mucosae, specifically the genital tract, is characterized by binding and, in some studies, neutralizing HIV-specific IgG and IgA antibodies. Ample evidence, however, points to discrepancies and difficulties in the detection of HIV-specific IgA in HIV-positive subjects, and an even more pronounced divide surfaces in studies done with individuals exposed to HIV, but uninfected. Reports in the literature detail HIV-specific (in some cases, neutralizing) IgA antibodies, in the absence of specific IgG, in the serum and mucosal secretions of virus-exposed, seronegative subjects; this has given rise to speculation that HIV-specific IgA provides a protective immune response to the virus in high-risk individuals who remain seronegative. Contradictory results, however, describe the absence of both IgA and IgG HIV antibodies in the mucosal secretions of similar cohorts. Considering the importance of the antibody response to ascertaining the correlates of HIV immunity, as well as on vaccine research and development, this review addresses the relevant studies and their implications.

CD4+ T‐cell immunity in the female genital tract is critically dependent on local mucosal immunization

“…immunization, irrespective of the hormonal cycle [3]. Antibodies in genital tract secretions most likely represent both serum derived and locally produced antibodies [14,15] and in contrast to other mucosal tissues, IgG antibodies dominate over IgA antibodies in genital tract secretions (reviewed [16]). …”

Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

“…Studies have shown that IgG, rather than IgA, is the most abundant immunoglobulin present in the semen of healthy men. 94,169 Furthermore, the distribution of IgA subclasses indicated the presence of secretory IgA, polymeric IgA and monomeric IgA. 94 Effects of hormones on testicular immune responses Androgens, namely testosterone, have immunosuppressive functions and have been shown to reduce TLR-4 expression in testicular macrophages.…”

Induction of Potent and Long-Lived Antibody and Cellular Immune Responses in the Genitorectal Mucosa Could be the Critical Determinant of HIV Vaccine Efficacy

“…These observations immediately prompt the need to further investigate the role of IgA in HIV-1 acquisition since it has been significantly associated with mucosal immunity to HIV-1 in several studies of HEPS (188, 190, 192). Moreover, these observations indicate that protection from infection is not necessarily mediated by neutralizing antibodies or robust CTLs as inferred from studies in HEPS, elite controllers, and LTNPs, thus emphasizing the need to re-define correlates of protection, and perhaps keenly study the role of non-neutralizing antibodies in protection versus risk.…”