Cervical HIV-Specific IgA in a Population of Commercial Sex Workers Correlates with Repeated Exposure But Not Resistance to HIV

Abstract

We conducted a comprehensive cross-sectional analysis of total and HIV-specific cervical antibody levels in HIV-1-resistant, uninfected, and infected women in order to examine the role of HIV-specific antibody responses in the female genital tract and examine the effect on antibody levels of various epidemiologic factors in this population. Cervical lavages were collected from 272 subjects of the Pumwani commercial sex worker cohort. Total and HIV-specific genital tract IgA and IgG levels were measured using an ELISA and correlated with behavioral and demographic factors. No significant difference was seen between cervical HIV-specific IgA levels in infected, uninfected, and resistant individuals, nor were any correlations between cervical HIV-specific IgA and neutralization capacity or viral shedding seen. We did, however, note increased HIV-specific IgA in HIV-negative women with four or more clients per day, and decreased HIV-specific IgA in both long-term nonprogressors and long-term survivors. These results show that there is not a strong cohort-wide correlation between HIV-specific cervical IgA levels and resistance to infection by HIV-1 as previously believed, but there is a correlation between exposure to HIV and HIV-specific cervical IgA. Our findings do not preclude the possibility that functional differences in the cervical IgA of HEPS women may play a role in resistance, but argue that HIV-specific responses may not be a universal protective factor. They also indicate that resistance to HIV is a complex condition related to more factors than exposure. Further studies of correlates of immune protection in these individuals would be beneficial to the field.

The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

“…30,43 -45 Thus far, there is no firm evidence of an association or causal relationship between virus-specific IgA and natural resistance to HIV in EU individuals. 46 However, HIV-reactive IgA from such cohorts has exhibited the ability to neutralize HIV 29,31,32 and inhibit syncytia formation. 30 With particular interest to mucosal protection, cervicovaginal lavage-derived secretory IgA from EU can inhibit virus transcytosis in vitro .…”

HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis

“…In addition, recent identification of HIV-1-specific antibodies as a potential correlate of protection from HIV-1 infection in the RV144 vaccine trial (9) has led to an intensive focus on anti-HIV-1 humoral immunity, with increasing interest in the mucosal humoral response and its role in protection from HIV-1 infection. Some studies have not found mucosal IgA that either binds to or neutralizes HIV-1 (10-13), yet others have reported that HIV-1-exposed seronegative (HESN) women have measurable levels of anti-HIV-1 IgA responses in cervicovaginal secretions (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Specifically, elevated levels of secretory IgA within the female reproductive tract were found to be associated with host resistance to HIV-1 among HIV-1-exposed uninfected commercial sex workers with a large number of clients per day (19).…”

“…Some studies have not found mucosal IgA that either binds to or neutralizes HIV-1 (10-13), yet others have reported that HIV-1-exposed seronegative (HESN) women have measurable levels of anti-HIV-1 IgA responses in cervicovaginal secretions (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Specifically, elevated levels of secretory IgA within the female reproductive tract were found to be associated with host resistance to HIV-1 among HIV-1-exposed uninfected commercial sex workers with a large number of clients per day (19). Furthermore, genital HIV-neutralizing IgA was associated with reduced HIV-1 acquisition (18), and HESN women were five times more likely to have neutralizing IgA in cervicovaginal secretions than low-risk control women (23).…”

Mucosal Immune Regulation: Does it Help Thwart HIV?

“…However, the protective role of cervical IgA in HIV acquisition remains controversial. While some studies have reported a higher proportion of cervical IgA [95][96][97] among HESN CSWs and discordant couples, others reported its absence [98,99] or correlated its frequency at FGT with higher daily exposure to the virus [95,100]. Hence, it is still unclear to what extent cervical IgA protects against HIV.…”