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.
Highlights
Each year, 2.6 million deaths occur during the neonatal period, with infectious diseases being the leading cause of mortality, in low-income countries [1, 2]
Our comprehensive analysis of maternal and cord plasma total IgG and IgG subclasses against a wide range of microbial and vaccine antigens allowed a deep immunoprofiling, that is essential to decipher the mechanisms affecting antibody placental transfer and maternal and newborn immunity in women chronically exposed to pathogens
Subclass levels are the corresponding maternal antibody levels, and that maternal HIV infection is associated with a reduction of total IgG levels in the cord due to low maternal levels, and to a reduction of IgG and IgG1 placental transfer
Summary
2.6 million deaths occur during the neonatal period, with infectious diseases being the leading cause of mortality, in low-income countries [1, 2]. Transplacental Transfer of IgG Subclasses [3,4,5,6]. Microorganisms such as respiratory syncytial virus (RSV) cause no or mild disease in adults but induce acute bronchiolitis, viral pneumoniae, and croup in infants, with those between 2 and 6 months of age at the highest risk, especially in low-income countries [7, 8]. Acquisition of immunity from vaccination is not immediate and vaccines are not available for all infectious diseases. Newborns mostly rely on the protection elicited by maternal antibodies transferred across the placenta, which provide passive immunity against common pathogens [14]
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