Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

Abstract

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors.

Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya

“…Similarly, the trend of cord to maternal antibody transfer ratio showed a decrease with HIV infection. These findings are in line with previous studies 25 which together raise concerns involving the effectiveness of a maternal RSV vaccine introduction to low-and middle-income countries (LMICs), which is thought might be negatively impacted by the existing comorbidities.…”

Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV

“…The discrepancies between studies could be multifactorial, including methodology, different maternal ART coverage, different exposure to pathogens, the geographical areas, and the timing of infants analysis. One of the strengths of this study is that we determined IgG concentrations from the blood of 6-week old infants, which significantly differ from cord blood, the source used in most of the studies in this field [ 5 , 7 , 10 , 12 , 14 – 16 , 34 , 35 ]. Cord blood samples composition mostly reflects fetal rather than neonatal characteristics [ 17 , 37 , 38 ]; for instance, in cord blood generally, there are higher IgG levels than in mothers [ 39 ].…”

“…The main determinants of infant IgG profile, at 6 weeks of life, are the maternal IgG levels and distribution [ 14 , 18 ]. In our study, we did not evaluate maternal samples, but it is well known that hypergammaglobulinemia and maternal immunological dysfunctions in the B compartment are common in African pregnant women living with HIV [ 5 , 6 , 10 ], and that the polyclonal B cell activation persist even after prolonged antiretroviral treatment [ 24 , 25 ].…”

“…In our study the lack of correlations between total IgG and anti-PCP IgG (and of IgG2 and anti-PCP-IgG2) was observed in both groups, suggesting a differential efficiency in the mechanism of IgG transplacental passage. Differences in the efficiency of transfer based on IgG subclasses structures and types of antigen-specific immunoglobulins has been previously reported [ 14 , 27 ]. Contrasting results have been obtained in different studies on HEU infants: some reported reduction in transfer of specific antibodies against H. influenzae , diphtheria, pertussis, pneumococcus, measles, tetanus, and Plasmodium falciparum [ 10 , 12 , 16 , 29 , 34 , 35 ], but others did not find any effect [ 15 , 36 ].…”

“…Although the underlying mechanisms are not fully elucidated, it has been suggested that IgG levels over 15 g/l can cause the saturation of FcRN receptors, which mediate the IgG transplacental passage [ 8 ], and indeed, in clinical studies, maternal IgG levels over 15 g/l have been associated with abnormal IgG concentrations in HEU infants [ 9 , 10 ]. Impairments of IgG transfer in HEU infants have been observed by some authors [ 5 , 11 – 14 ], but others reported similar IgG levels in HIV-exposed and -unexposed infants [ 15 , 16 ], or described a differential IgG passage depending on the characteristics of pathogen-specific antibodies [ 14 ]. The difficulty to obtain consistent results can be due to different causes, such as the timing of blood sampling (most of the mother/infant pairs studies have used cord blood whose composition mostly reflect fetal rather than neonatal condition [ 17 ]), or the lack of reference levels in healthy African infants.…”