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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Quantifying maternally derived respiratory syncytial virus specific neutralising antibodies in a birth cohort from
Joyce U Nyiro1, Charles Sande1, Martin Mutunga1
1Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.
Insights
Maternal vaccination could protect infants from severe respiratory syncytial virus (RSV) disease. RSV neutralising antibody titres in infants decay rapidly, approximately halving each month, regardless of initial levels.
Area of Science:
- Immunology
- Vaccinology
- Pediatrics
Background:
- Severe respiratory syncytial virus (RSV) disease disproportionately affects infants under six months.
- No licensed RSV vaccine currently exists, necessitating alternative protection strategies.
- Maternal vaccination is a potential strategy to confer passive immunity to infants.
Purpose of the Study:
- To determine the levels and kinetics of functional RSV-specific antibodies in infants.
- To inform the design of maternal RSV vaccines for infant protection.
- To analyze antibody decay rates in the first year of life.
Main Methods:
- Analysis of cord blood and serial blood samples from 100 infants in a Kenyan birth cohort.
- Measurement of RSV neutralizing antibodies using the logarithm (base 2) plaque reduction neutralization test (PRNT).
- Linear regression analysis accounting for within-person clustering to assess antibody decay.
Main Results:
- The geometric mean neutralizing antibody titre at birth was 10.6 (log2PRNT).
- Antibody titres exhibited a log-linear decay with an estimated half-life of 36 days.
- Cord titres showed seasonal variation, correlating with community RSV transmission patterns.
Conclusions:
- Infant RSV neutralizing antibody titres decrease by approximately half each month.
- The rate of antibody decay is highly individual but not dependent on initial cord titre.
- Seasonal fluctuations in RSV-specific cord titres suggest maternal antibody boosting.
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.
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