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

Joyce U Nyiro,Amek Nyaguara,James A Berkley,Godfrey Bigogo,Nancy Otieno,Jennifer R Verani,Bryan Nyawanda,D James Nokes,Nickson Murunga,Hope Mwangudza,Elizabeth Bukusi,Dufton Mwaengo,Calleb Odundo,Marc-Alain Widdowson,Sandra S Chaves,Patrick Munywoki

doi:10.12688/wellcomeopenres.17636.1

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 transfer 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.

Highlights

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (LRTI) among infants leading to hospital admissions and in-hospital deaths, with 99% of these deaths occurring in developing countries[1]
We describe background factors and illness episodes occurring during pregnancy that could influence transplacental transfer of respiratory syncytial virus (RSV)-specific antibodies to support the successful implementation of a maternal RSV vaccine program in Kenya
In this study, we found Kenyan women from the two geographical regions of Siaya and Kilifi differing in many characteristics, but these differences did not affect the mean levels of RSV-specific antibodies transferred to infants or the overall efficiency of transplacental transfer

Summary

Introduction

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (LRTI) among infants leading to hospital admissions and in-hospital deaths, with 99% of these deaths occurring in developing countries[1]. Severe RSV-associated LRTI is most common among infants under six months of age[3,4], resulting in about 32% of hospitalised infants in the rural coast of Kenya, during epidemics[3]. Maternal immunisation is currently being considered as a strategy to protect infants from severe RSV-associated disease because of the lack of licenced RSV vaccines targeting infants. Despite the advancement in development of maternal RSV vaccines, the success of this program will depend on how efficiently vaccine-induced RSV-specific antibodies are transferred to the infant. 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. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. At enrollment the median age was 25 years

Methods

Results

Discussion

Conclusion