Lack of Correlation Between Vertical Transmission of HIV-1 and Maternal Antibody Titers Against Autologous Virus in Human Monocyte-Derived Macrophages

Mabondzo, Aloı̈se; Narwa, Rémy; Roques, Pierre; Gs, Gras; Hervé, François; Parnet-Mathieu, F; Lasfargues, G; Courpotin, C; Dormont, Dominique

doi:10.1097/00042560-199801010-00015

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…However, the observation of higher IC 50 s in transmitting mothers than in nontransmitting mothers makes our hypothesis that transmitting mothers have weaker NAb responses (more resistant viruses) less likely. Similar to our results, a number of older studies using primary isolates to assess the overall neutralization sensitivity of the virus population observed no difference in the titers of NAbs against autologous virus and the risk of transmission ( 10 , 13 , 21 – 24 , 27 ). However, other studies using similar methods did report higher levels of autologous NAbs in nontransmitting mothers ( 7 , 8 , 11 , 12 ).…”

Section: Discussionsupporting

confidence: 91%

Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk

Milligan

Omenda

Chohan

et al. 2016

mBio

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Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission. Ten transmitting and 10 nontransmitting HIV-infected mothers at high risk of MTCT were included in this study. Full-length HIV envelope genes (n = 100) were cloned from peripheral blood mononuclear cells obtained near transmission from transmitting mothers and at similar time points from nontransmitting mothers. Envelope clones were tested as pseudoviruses against contemporaneous, autologous maternal plasma in neutralization assays. The association between transmission and the log2 50% inhibitory concentration (IC50) for multiple virus variants per mother was estimated by using logistic regression with clustered standard errors. t tests were used to compare proportions of neutralization-resistant viruses. Overall, transmitting mothers had a median IC50 of 317 (interquartile range [IQR], 202 to 521), and nontransmitting mothers had a median IC50 of 243 (IQR, 95 to 594). Transmission risk was not significantly associated with autologous NAb activity (odds ratio, 1.25; P = 0.3). Compared to nontransmitting mothers, transmitting mothers had similar numbers of or fewer neutralization-resistant virus variants, depending on the IC50 neutralization resistance cutoff. In conclusion, HIV-infected mothers harbor mostly neutralization-sensitive viruses, although resistant variants were detected in both transmitting and nontransmitting mothers. These results suggest that MTCT during the breastfeeding period is not driven solely by the presence of maternal neutralization escape variants.

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Section: Discussionsupporting

confidence: 91%

Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk

Milligan

Omenda

Chohan

et al. 2016

mBio

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“…Our data support the findings of Kliks et al and Scarlatti et al [16,17], who found a higher percentage of mothers with autologous neutralizing antibody among the nontransmitter group. Husson et al and Mabondzo et al [18,19], however, failed to identify an increased number of nontransmitters with autologous neutralizing antibody. Additionally, in all reports, at University of Ulster at Coleraine on April 12, 2015 http://jid.oxfordjournals.org/ Downloaded from including our own, there were nontransmitters without detectable autologous neutralizing antibody.…”

Section: Discussionmentioning

confidence: 99%

Lack of Autologous Neutralizing Antibody to Human Immunodeficiency Virus Type 1 (HIV‐1) and Macrophage Tropism Are Associated with Mother‐to‐Infant Transmission

et al. 1999

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To investigate factors that affect mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), autologous neutralizing antibody, viral load, and viral tropism were evaluated in 28 pregnant women infected with HIV-1, of whom 8 were transmitters and 20 nontransmitters. One (12%) of 8 transmitters versus 11 (55%) of 20 nontransmitters had autologous neutralizing antibody (P=.04). Plasma levels of HIV-1 RNA and infectious HIV-1 titers (mean+/-SD) in peripheral blood mononuclear cells (PBMC) at delivery did not differ significantly between transmitters and nontransmitters (24, 266+/-10,101 vs. 31,589+/-9128 copies/mL and 29+/-12 vs. 42+/-17 infected cells per 106 PBMC, respectively). However, only transmitters (4 [50%] of 8) were HIV p24 antigen positive. The ability of HIV-1 strains to induce syncytium did not differ between groups (P=.6); however, only non-syncytium-inducing isolates were transmitted. Isolates from 4 (80%) of 5 transmitters versus 2 (18%) of 12 nontransmitters (P=.03) demonstrated increasing replication in macrophages. Thus, lack of autologous neutralizing antibody and increased replication in macrophages were significantly associated with mother-to-infant transmission. In addition, autologous neutralizing antibody was associated with reduced viral load.

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“…Supporting this model, a few studies have suggested that transmitted viruses are escape variants resistant to neutralization by maternal antibodies [80-82,102,103]. However, other studies did not confirm these findings [88,89,95,104-106]. The observed discordant results may be due to small sample sizes, disparate maternal and infant sample collection time points, and a lack of identification of the route of transmission in several studies ( in utero , in absence or in presence of only low levels of IgG, versus perinatally or early postpartum, in presence of high levels of IgG).…”

Section: Reviewmentioning

confidence: 98%

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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Lack of Correlation Between Vertical Transmission of HIV-1 and Maternal Antibody Titers Against Autologous Virus in Human Monocyte-Derived Macrophages

Cited by 8 publications

References 13 publications

Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk

Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk

Lack of Autologous Neutralizing Antibody to Human Immunodeficiency Virus Type 1 (HIV‐1) and Macrophage Tropism Are Associated with Mother‐to‐Infant Transmission

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

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