Quantifying maternally derived respiratory syncytial virus specific neutralising antibodies in a birth cohort from coastal Kenya

Joyce U Nyiro,Charles Sande,Martin Mutunga,Patience K Kiyuka,Patrick K Munywoki,J Anthony G Scott,D James Nokes

doi:10.1016/j.vaccine.2015.02.039

Abstract

BackgroundSevere respiratory syncytial virus (RSV) disease occurs predominantly in children under 6 months of age. There is no licensed RSV vaccine. Protection of young infants could be achieved by a maternal vaccine to boost titres of passively transferred protective antibodies. Data on the level and kinetics of functional RSV-specific antibody at birth and over the early infant period would inform vaccine product design. MethodsFrom a birth cohort study (2002–2007) in Kilifi, Kenya, 100 participants were randomly selected for whom cord blood and 2 subsequent 3-monthly blood samples within the first year of life, were available. RSV antibodies against the A2 strain of RSV were assayed and recorded as the logarithm (base 2) plaque reduction neutralisation test (PRNT) titre. Analysis by linear regression accounted for within-person clustering. ResultsThe geometric mean neutralisation antibody titre was 10.6 (SD: 1.13) at birth with a log-linear decay over the first 6 months of life. The estimated rate of decay was −0.58 (SD: 0.20) log2PRNT titre per month and a half-life of 36 days. There was no significant interaction between cord titre and rate of decay with age. Mean cord titres rose and fell in a pattern temporally tracking community virus transmission. ConclusionsIn this study population, RSV neutralising antibody titres decay approximately two-fold every one month. The rate of decay varies widely by individual but is not related to titre at birth. RSV specific cord titres vary seasonally, presumably due to maternal boosting.

Highlights

Severe respiratory syncytial virus (RSV) disease occurs predominantly in children under 6 months of age
RSV disease may be responsible for nearly 200,000 deaths per year in young children and 99% of these deaths occur in low income countries [2]
Prevention of RSV disease is primarily targeted towards young infants [4], for which two vaccine strategies are appropriate: first, to vaccinate infants at the earliest age when able to develop a protective immune response with minimal reactogenicity, and second, to boost the level of RSV-specific antibodies in pregnant women before delivery to extend the duration of protective antibodies in early infancy [5,6,7]

Summary

Introduction

Severe respiratory syncytial virus (RSV) disease occurs predominantly in children under 6 months of age. Results: The geometric mean neutralisation antibody titre was 10.6 (SD: 1.13) at birth with a log-linear decay over the first 6 months of life. Severe RSV disease occurs primarily in infancy and predominantly among children 1–5 months of age [1]. Prevention of RSV disease is primarily targeted towards young infants [4], for which two vaccine strategies are appropriate: first, to vaccinate infants at the earliest age when able to develop a protective immune response with minimal reactogenicity, and second, to boost the level of RSV-specific antibodies in pregnant women before delivery to extend the duration of protective antibodies in early infancy [5,6,7].

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Results

Discussion

Conclusion