Maternal Human Immunodeficiency Virus-Associated Hypergammaglobulinemia Reduces Transplacental Transfer of Immunoglobulin G to Plasmodium falciparum Antigens in Cameroonian Neonates

Babakhanyan, Anna; Ekali, Gabriel Loni; Dent, Arlene E.; Kazura, James W.; Nguasong, John Tamo; Fodjo, Barriere A. Y.; Yuosembom, Emile K.; Esemu, Livo F.; Taylor, Diane Wallace; Leke, Rose G. F.

doi:10.1093/ofid/ofw092

Cited by 16 publications

(33 citation statements)

References 45 publications

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“…In contrast, Moro et al found that HIV+ Mozambican women (receiving no ART) had reduced CMR of antibodies against MSP1, Pf lysate, AMA1, and EBA175 [26]. HIV+ Cameroonian women who received only nevirapine at delivery had decreased CMRs to CSP, AMA1, MSP1, and tetanus compared with HIV- women [47]. This was thought to be driven by elevated hypergammaglobulinemia in HIV+ women, but after adjusting for this, decreased CMR of CSP, MSP1, and tetanus persisted.…”

Section: Discussionmentioning

confidence: 99%

“…A limitation of this study is that we did not measure IgG subclasses to vaccine or Pf antigens, which might have increased our ability to detect differences in CMRs according to maternal HIV or malaria infection, as observed in some studies that detected significant differences in antimalarial IgG1 and IgG3 CMRs but not in total antimalarial IgG [26, 47]. Additionally, baseline differences between HIV+ and HIV- women (most notably age and gravidity) affect their risk for malaria during pregnancy in that younger and primi- or secundi-gravidae women are at highest risk [50].…”

Section: Discussionmentioning

confidence: 99%

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Reduced Transplacental Transfer of Antimalarial Antibodies in Kenyan HIV-Exposed Uninfected Infants

Ray

Dobbs

Ogolla

et al. 2019

Open Forum Infectious Diseases

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Background Altered neonatal immune responses may contribute to the increased morbidity observed in HIV-exposed but uninfected (HEU) infants compared with HIV-unexposed uninfected (HUU) infants. We sought to examine the effects of prenatal HIV and malaria exposure on maternal and neonatal plasma cytokine profiles and transplacental antibody transfer. Methods Forty-nine HIV+ and 50 HIV- women and their HIV-uninfected neonate pairs from Kenya were assessed. All HIV+ mothers received combination antiretroviral therapy. Maternal plasma and cord blood plasma samples at delivery were tested for 12 cytokines, total IgG, and IgG specific to 4 vaccine antigens and 14 Plasmodium falciparum antigens. Results HIV+ mothers had lower levels of all 12 plasma cytokines at delivery compared with HIV- mothers, but there were no differences between HEU and HUU neonates. There were no differences in the cord-to-maternal ratios (CMRs) of vaccine-specific IgG between HIV+/HEU and HIV-/HUU maternal–neonate pairs. HIV+/HEU maternal–neonate pairs had significantly lower CMRs for 3 antimalarial IgGs—merozoite surface protein 9, circumsporozoite protein, and erythrocyte binding antigen 181—which remained statistically significant after adjustment for malaria in pregnancy. Conclusions In a cohort of optimally treated HIV-infected pregnant women, maternal HIV infection was associated with reduced transplacental transfer of antimalarial antibodies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduced Transplacental Transfer of Antimalarial Antibodies in Kenyan HIV-Exposed Uninfected Infants

Ray

Dobbs

Ogolla

et al. 2019

Open Forum Infectious Diseases

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“…Plasma IgG Ab levels to VAR2CSA recombinant proteins (FV2 and DBL5) of the FCR3 strain, expressed in Baculovirus-transfected insect cells, were measured using a multi-analyte platform (MAP). The coupling of the recombinant proteins to MagPix microspheres and basic protocol have been described previously [21,24,25]. Briefly, 50 μl of antigen-coupled microspheres (2000 microspheres/antigen) were incubated in a well of a microtiter plate (U-bottom microplate) with 50 μl of plasma diluted to 1:100 in phosphate buffered saline containing 1% bovine serum albumin (PBS 1% BSA) for 1 h at room temperature on a rotating shaker at 500 rpm (Microplate Shaker, Lab-line, Melrose Park, IL, USA).…”

Section: Measurement Of Antibodiesmentioning

confidence: 99%

Antibodies to full-length and the DBL5 domain of VAR2CSA in pregnant women after long-term implementation of intermittent preventive treatment in Etoudi, Cameroon

et al. 2020

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In high malaria transmission settings, the use of sulfadoxine-pyrimethamine-based intermittent preventive treatment during pregnancy (IPTp-SP) has resulted in decreased antibody (Ab) levels to VAR2CSA. However, information of Ab levels in areas of low or intermediate malaria transmission after long-term implementation of IPTp-SP is still lacking. The present study sought to evaluate antibody prevalence and levels in women at delivery in Etoudi, a peri-urban area in the capital of Yaoundé , Cameroon, that is a relatively low-malaria transmission area. Peripheral plasma samples from 130 pregnant women were collected at delivery and tested for IgG to the full-length recombinant VAR2CSA (FV2) and its most immunogenic subdomain, DBL5. The study was conducted between 2013 and 2015, approximately ten years after implementation of IPTp-SP in Cameroon. About 8.6% of the women attending the clinic had placental malaria (PM). One, two or 3 doses of SP did not impact significantly on either the percentage of women with Ab to FV2 and DBL5 or Ab levels in Ab-positive women compared to women not taking SP. The prevalence of Ab to FV2 and DBL5 was only 36.9% and 36.1%, respectively. Surprisingly, among women who had PM at delivery, only 61.5% and 57.7% had Ab to FV2 and DBL5, respectively, with only 52.9% and 47.1% in PM-positive paucigravidae and 77.7% of multigravidae having Ab to both antigens. These results suggest that long-term implementation of IPTp-SP in a lowmalaria transmission area results in few women having Ab to VAR2CSA.

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“…The effect of maternal HIV infection is also controversial. Some studies demonstrated that HIV infection leads to a reduction of the transplacental transfer of Hib , diphtheria, pertussis, pneumococcus, measles, tetanus, and Plasmodium falciparum ( P. falciparum ) specific antibodies ( 28 , 29 , 39 – 45 ), but others have shown no effect ( 29 , 33 , 38 , 41 , 42 , 46 ). Those studies had several limitations, as the numbers of antigens tested and HIV-infected women included in the analyses were low.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Maternal Human Immunodeficiency Virus-Associated Hypergammaglobulinemia Reduces Transplacental Transfer of Immunoglobulin G to Plasmodium falciparum Antigens in Cameroonian Neonates

Cited by 16 publications

References 45 publications

Reduced Transplacental Transfer of Antimalarial Antibodies in Kenyan HIV-Exposed Uninfected Infants

Reduced Transplacental Transfer of Antimalarial Antibodies in Kenyan HIV-Exposed Uninfected Infants

Antibodies to full-length and the DBL5 domain of VAR2CSA in pregnant women after long-term implementation of intermittent preventive treatment in Etoudi, Cameroon

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

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