The Breadth and Titer of Maternal HIV-1-Specific Heterologous Neutralizing Antibodies Are Not Associated with a Lower Rate of Mother-to-Child Transmission of HIV-1

Chaillon, Antoine; Wack, Thierry; Braibant, Martine; Mandelbrot, Laurent; Blanche, Stéphane; Warszawski, Josiane; Barin, Françis

doi:10.1128/jvi.00518-12

Cited by 14 publications

(9 citation statements)

References 43 publications

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“…Indeed we found that NAbs toward a CRF01-AE isolate, MBA, were significantly associated with a lower rate of MTCT in Thailand. Similarly, statistically significant higher frequencies or titers of NAbs toward several strains were observed in non-transmitting mothers in our French study when the clade B-infected mothers or non clade-B-infected mothers were analyzed separately [109]. Collectively, these data suggest that particular HIV-1 variants may provide a measure of protective antibodies depending of the population.…”

Section: Reviewsupporting

confidence: 59%

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

Braibant

Barin

2013

Retrovirology

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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.

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Section: Reviewsupporting

confidence: 59%

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

Braibant

Barin

2013

Retrovirology

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“…However, not all studies established this association (2,3). Several studies reported more potent HIV-1-neutralizing Ab responses in nontransmitting mothers compared with those in transmitting mothers (4) as well as transmission of neutralization escape variants (5)(6)(7)(8), yet other studies did not (9)(10)(11). These disparate results may be due to small cohort sizes, distinct timing of infant HIV-1 diagnosis, and inadequate control of major nonimmune risk modifiers of transmission.…”

Section: Introductionmentioning

confidence: 56%

Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission

Permar¹,

Fong²,

Vandergrift³

et al. 2015

J. Clin. Invest.

112

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“…However, other studies did not confirm this association (18,19). Studies have also evaluated the association of maternal plasma neutralization breadth and MTCT risk with inconclusive results (20,21). To gain a deeper understanding of the role of maternal protective antibody (Ab) responses during MTCT, our group recently conducted a comprehensive maternal humoral correlate of risk against MTCT of HIV using samples from the historic Women and Infant Transmission Study (WITS), a North American clade B infection cohort that was enrolled prior to the availability of ART (22).…”

Section: Importancementioning

confidence: 89%

Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk

Martinez

Vandergrift²,

Douglas³

et al. 2017

J Virol

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The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV to the infant. We previously determined that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy-to-neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U.S. Woman and Infant Transmission Study (WITS) cohort. Here, we defined the fine specificity and function of the potentially protective maternal V3-specific IgG antibodies associated with reduced peripartum HIV transmission risk in this cohort. The V3-specific IgG binding that predicted low risk of mother-to-child-transmission (MTCT) was dependent on the C-terminal flank of the V3 crown and particularly on amino acid position 317, a residue that has also been associated with breakthrough transmission in the RV144 vaccine trial. Remarkably, the fine specificity of potentially protective maternal plasma V3-specific tier 1 virus-neutralizing responses was dependent on the same region in the V3 loop. Our findings suggest that MTCT risk is associated with neutralizing maternal IgG that targets amino acid residues in the C-terminal region of the V3 loop crown, suggesting the importance of the region in immunogen design for maternal vaccines to prevent MTCT. IMPORTANCE Efforts to curb HIV-1 transmission in pediatric populations by antiretroviral therapy (ART) have been highly successful in both developed and developing countries. However, more than 150,000 infants continue to be infected each year, likely due to a combination of late maternal HIV diagnosis, lack of ART access or adherence, and drug-resistant viral strains. Defining the fine specificity of maternal humoral responses that partially protect against MTCT of HIV is required to inform the development of a maternal HIV vaccine that will enhance these responses during pregnancy. In this study, we identified amino acid residues targeted by potentially protective maternal V3-specific IgG binding and neutralizing responses, localizing the potentially protective response in the C-terminal region of the V3 loop crown. Our findings have important implications for the design of maternal vaccination strategies that could synergize with ART during pregnancy to achieve the elimination of pediatric HIV infections.KEYWORDS HIV, mother-to-child transmission, V3, antibodies

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The Breadth and Titer of Maternal HIV-1-Specific Heterologous Neutralizing Antibodies Are Not Associated with a Lower Rate of Mother-to-Child Transmission of HIV-1

Cited by 14 publications

References 43 publications

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission

Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk

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