Evidence for Efficient Vertical Transfer of Maternal HIV-1 Envelope-Specific Neutralizing Antibodies but No Association of Such Antibodies with Reduced Infant Infection.
ABSTRACT Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. We compared antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breastfeeding transmission pairs. The Envelope binding titers were strongly correlated (r=0.91, p<0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, p<0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and non-transmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.
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ABSTRACT: Although antiretroviral (ARV) prophylaxis can reduce mother-to-child transmission (MTCT) of HIV-1 to less than 2%, one-quarter of a million infants continue to be infected with HIV-1 annually. ARV prophylaxis alone will fail to eliminate infant HIV-1 infection because of issues of maternal adherence, toxicities, ARV-resistant virus strains, and acute maternal infection. Effective maternal and/or infant immunization will likely be required to achieve the goal of an HIV-free generation. This article describes recent studies of antibody responses that protect against vertical HIV-1 transmission. Studies have shown that maternal neutralization breadth is not a critical factor in MTCT, yet the ability of maternal plasma to neutralize autologous virus variants may be important in infant protection. There is also new evidence that infants mount robust and durable antibody responses to HIV-1 envelope following vaccination and can develop broad neutralization during infection. Finally, passive immunization of infants with highly potent and broad neutralizing antibodies may be an effective strategy to protect infants against infection with postnatally transmitted variants. Defining the characteristics of maternal and infant antibody responses that protect against MTCT will inform development of effective passive and active immunization strategies that will likely be required to eliminate pediatric HIV-1.Current Opinion in HIV and AIDS 02/2015; 10(3). DOI:10.1097/COH.0000000000000150 · 4.39 Impact Factor
PLoS Pathogens 08/2014; 10(8):e1004283. DOI:10.1371/journal.ppat.1004283 · 8.14 Impact Factor
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ABSTRACT: In most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs migh confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1.Retrovirology 10/2013; 10(1):103. DOI:10.1186/1742-4690-10-103 · 4.77 Impact Factor