Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

Joyce Uchi Nyiro,Martin Mutunga,David James Nokes,Patrick Kioo Munywoki,Charles Jumba Sande,John Anthony G Scott,Patience Kerubo Kiyuka,John S Tregoning

doi:10.1371/journal.pone.0166706

Abstract

BackgroundThe target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development.MethodsA case control study nested in a birth cohort (2002–07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres.ResultsThe mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3).ConclusionsFrom this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

Highlights

Respiratory syncytial virus (RSV) is the most common viral cause of severe acute lower respiratory infections among children aged less than 5 years [1,2,3]
Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease
The odds of RSV disease decreased with increase in log2PRNT cord blood titre

Summary

Introduction

Respiratory syncytial virus (RSV) is the most common viral cause of severe acute lower respiratory infections among children aged less than 5 years [1,2,3]. A target group for RSV prevention is children under 6 months old who are highly susceptible to severe RSV associated disease[4]. An alternative approach currently under consideration as a means of protecting the vulnerable infant from RSV disease during the first few months of life is through vaccine boosting of maternal RSV-specific antibodies. The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development.

Methods

Discussion

Conclusion