Mother to child transmission of HIV‐1 in a Thai population: Role of virus characteristics and maternal humoral immune response

Abstract

The objective of this study was to investigate factors influencing mother to child transmission of HIV-1 in Thailand, where HIV-1 CRF01_AE, the major subtype in Southeast Asia, predominates. Samples from 84 HIV-1 infected, anti-retroviral treatment-naïve, non-breast feeding mothers, 28 who transmitted HIV-1 to their babies (transmitters) and 56 who did not (non-transmitters), were studied for maternal humoral immune response and virus characteristics. Maternal humoral immune response was measured by lymphocyte phenotyping; neutralizing antibodies to laboratory HIV-1 MN strain and two clinical isolates; peptide binding antibody to gp41 and V3 from strains CRF01_AE, B, and MN; autologous antibodies; and quasispecies diversity. Virus characteristics studied were viral load, co-receptor usage, and viral replication capacity. No significant difference between transmitters and non-transmitters was found for any parameter of maternal humoral immune response. However, viral load and viral replication capacity were significantly higher in transmitters versus non-transmitters and were not correlated with each other. This suggests that viral replication capacity may be a transmission factor independent of viral load, which is already well established as a risk factor for transmission of HIV-1. All except four viral isolates used the CCR5 co-receptor. This is one of few studies of vertical transmission in a population where HIV-1 CRF01_AE predominates. The data suggest that in this population the maternal humoral immune response was not important in preventing transmission at parturition, but that virus characteristics were key factors, and that viral replication capacity may contribute to birth-associated mother to child transmission of HIV-1.

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

“…In support of this hypothesis, previous studies reported that viruses transmitted during breastfeeding are usually resistant to maternal autologous neutralization [27,32]. However, other studies did not observe increased resistance of infant viruses to neutralization by maternal plasma [14,63,69,70]. Furthermore, no difference in sensitivity to autologous neutralization was observed between clade C viruses from postnatally-infected infant and viruses from their mothers [28].…”

HIV-1 Autologous Antibody Neutralization Associates with Mother to Child Transmission

“…Although the FcRn receptor binds monomeric IgG more avidly than aggregated or immunocomplexed IgG the mechanism may provide a route whereby HIV-1/anti-HIV-1 IgG complexes can be transferred to the fetus [35]. Total IgG binding to gp160, gp120 glycoproteins and/or peptides derived from V3 or gp41 was measured in TM and NTM individuals with better binding found in the TM, which may be in line with heightened enhancement to transcytosis of HIV-1 via HIV/IgG complexes [12],[36]–[38]. In addition, it has been demonstrated in studies utilizing a trophoblast monolayer model mimicking the barrier between the placenta and fetal blood that the fusion of HIV-1 infected PBMCs, monocytes and macrophages at the apical side of the monolayer can be followed by HIV-1 transcytosis to the lateral side [35], [39].…”

“…Reports on human mother child pairs have shown better neutralization by NTM than by TM suggesting a protective role by Abs [24], [25]. Others report better neutralization by TM or find no differences between TM and NTM [12], [14], [18], [24], [26]–[29]. Neutralization resistance in children against mother’s plasma or serum has been reported suggesting transmission of neutralization escape mutants, but, in contrast, sensitivity for neutralization by plasma of the mother has also been found [18], [24], [26], [27], [30], [31].…”

“…The Env is also the major target of the host immune response and induces binding antibodies (Abs), some of which are neutralizing (NAbs) that can control or prevent infection [8]–[10]. There has been much speculation that viral fitness may determine MTCT with some studies showing that viruses from transmitting mothers (TM) possess higher replication capacities than viruses generated from non-transmitting mothers (NTM) [11], [12]. Two studies found no difference in infectivity between mothers and children’s env clones tested in a single-cycle assay [13], [14].…”

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

“…Animal studies have demonstrated that neutralizing antibodies elicited by a simian immunodeficiency virus (SIV) vaccine can at least slow disease progression (56), while direct administration of antibodies matched to the chal-lenge virus can block transmission (16,44). Studies of natural MCTC have yielded conflicting results (2,3,7,20,26,31,32,48), although possibly for identifiable reasons. The breadth of the neutralizing antibody response may depend on the subtype of HIV-1 being studied (5,10), and neutralizing antibody levels may be associated with the timing of transmission (3).…”