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

Abstract

Background: Severe 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.

Methods: From 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.

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. 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.

Conclusions: In 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.

Keywords: Birth cohort; Maternal antibody; Neutralisation; Rate of decay; Respiratory syncytial virus; Vaccine design.

Fig. 1

Frequency distribution of maternally transferred RSV specific antibodies (log₂ transformed PRNT titres) at birth for 100 infants born in Kilifi, Kenya. The overall mean (variance) and upper and lower quartile titres (log₂PRNT) are shown.

Fig. 2

The decay in PRNT titre (log base 2 transformed) over the first 6 months of life for a birth cohort, Kilifi, Kenya, with best fit linear decay model for all samples (mean) and for each quartile cord level (q1–q4) assuming a fixed rate of decay (−0.58 log₂PRNT titre per month).

Fig. 3

A histogram of the distribution of individual rates of decay showing the overall mean (standard deviation; inter-quartile range), −log₂PRNT/month.

Fig. 4

Dynamics of cord titres by time and transmission intensity. Grey symbols denote individual cord titres by date of birth, black square markers the mean cord titre by quarter (95% CI), and the vertical bars show the number of RSV IFAT positive paediatric severe or very severe pneumonia admissions to Kilifi District Hospital 2002–2008.