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

Abstract

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06–0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07–0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

Biological factors that may impair transplacental transfer of RSV antibodies: Implications for maternal immunization policy and research priorities for low- and middle-income countries

“…A more recent study assessing RSV CMR among 75 Alaska Native mother-infant pairs found that infants with CMR < 1.0 were more likely to be lower birth weight or preterm than infants with CMR > 1.0 [54] . Similar findings were noted in a recent study of pregnant women in Kenya [55] . In contrast, among a prospective cohort of 310 infants in rural Nepal, they did not find a statistically significant difference in RSV antibody transfer by GA in weeks, or between term and pre-term infants [27] .…”

“…HIV : Numerous studies in LMICs, including Bangladesh [71] , Botswana [72] , Brazil [58] , [73] , Cameroon [74] , Kenya [48] , [55] , [60] , [61] , [75] , Malawi [59] , Mozambique [70] , Nigeria [76] , and South Africa [77] , [78] , [79] , [80] , [81] have evaluated differences in maternal antibody levels and CMRs for various pathogens in cohorts of women with and without HIV. While there is some variation in findings across study settings, most show HIV-positive pregnant women have lower specific antibody titers during pregnancy compared to their HIV-negative peers and demonstrate impaired transplacental transfer, resulting in lower mean CMRs, lower mean antibody concentrations, and/or higher proportion of infants born with antibody levels below protective thresholds among their infants compared to those born to HIV-negative women.…”

Correlative outcomes of maternal immunization against RSV in cotton rats

“… 20 In a recent study on two cohorts of pregnant women from two cities in Kenya, it was shown that the efficiency of maternal transfer of antibodies, measured as cord to maternal titer ratio (CMTR) was reduced when the number of pregnancies was >6, indicating that some mechanisms of antibody transfer become less efficient as the number of viable pregnancies increased. 36 Although our results reflect only two pregnancies in cotton rats, our data might reflect a gradual reduction in the efficiency of transfer of antibodies from dams to pups that should be considered for further mechanistic studies, especially due to the impact that this can have on efficacy of human vaccinees.…”

Assessment of gestational age at antenatal care visits among Kenyan women to inform delivery of a maternal respiratory syncytial virus (RSV) vaccine in low- and middle-income countries

“…In Siaya County, additional data were collected from two hospitals, Bondo County Hospital and Siaya County Referral Hospital, leveraging on existing platform for surveillance of influenza disease among pregnant women. This surveillance is also led by KEMRI-CGHR in collaboration with US CDC 17 , 18 .…”