In the absence of intervention, only about one third of infants born to HIV-1 infected mothers who are continuously exposed to maternal breast milk over prolonged periods get infected. This observation raises the possibility that immune factors in infected women play a role in limiting HIV-1 transmission. Identifying factors associated with reduced HIV-1 transmission risk will improve our understanding on the potential correlates of protection that should be the focus of generating effective immunogens and vaccination protocols.
Researchers assessed the functional role of breast milk antibodies in a group of women with high plasma viral loads and systemic neutralizing Abs and determined that overall, breast milk contains low levels of neutralizing antibodies when compared to plasma. In contrast, they observed a robust non-neutralizing activity in breast milk that was associated with infant infection status. This study adds to the growing evidence of a potential role of non-neutralizing antibodies in limiting HIV-1 transmission and calls for more attention to this arm of the HIV-1 response.
HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads. (2012) PLoS Pathog 8(6): e1002739. doi:10.1371/journal.ppat.1002739
There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman’s autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS) – only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log10 lower (compared to 0.59 log10 lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001)and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk.