Passively Transmitted gp41 Antibodies in Babies Born from HIV-1 Subtype C-Seropositive Women: Correlation between Fine Specificity and Protection

Abstract

e HIV-exposed, uninfected (EUN) babies born to HIV-infected mothers are examples of natural resistance to HIV infection. In this study, we evaluated the titer and neutralizing potential of gp41-specific maternal antibodies and their correlation with HIV transmission in HIV-infected mother-child pairs. Specific gp41-binding and -neutralizing antibodies were determined in a cohort of 74 first-time mother-child pairs, of whom 40 mothers were infected with HIV subtype C. Within the infected mother cohort, 16 babies were born infected and 24 were PCR negative and uninfected at birth (i.e., exposed but uninfected). Thirty-four HIV-uninfected and HIV-unexposed mother-child pairs were included as controls. All HIV-positive mothers and their newborns showed high IgG titers to linear epitopes within the HR1 region and to the membrane-proximal (MPER) domain of gp41; most sera also recognized the disulfide loop immunodominant epitope (IDE). Antibody titers to the gp41 epitopes were significantly lower in nontransmitting mothers (P < 0.01) and in the EUN babies (P < 0.005) than in HIV-positive mother-child pairs. Three domains of gp41, HR1, IDE, and MPER, elicited antibodies that were effectively transmitted to EUN babies. Moreover, in EUN babies, epitopes overlapping the 2F5 epitope (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Our findings highlight important epitopes in gp41 that appear to be associated with exposure without infection and would be important to consider for vaccine design.

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants

“…Maternal antibodies are transferred to the fetus during pregnancy and, at birth, infants born to HIV-1 infected women have high levels of HIV-specific antibodies [30,64]. Furthermore, HIV Env-specific functional antibodies are present in the milk of HIV-infected women [31,65].…”

Response to letters on Bignami et al

“…This critique surprised us, as our group has a solid scientific reputation and a established clinical expertise in the field of MEU. [6][7][8] …”

A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles

“…Anti-MPER Abs with anti-viral activities were also described in mucosal secretions of highly-exposed but seronegative individuals (Kaul et al, 1999, 2001; Pastori et al, 2000; Devito et al, 2000a, 2000b; Tudor et al, 2009). Lastly, anti-MPER Abs that were passively passed through breast milk from infected mothers to their uninfected babies were correlated with protection (Diomede et al, 2012; Pollara et al, 2015). …”