Abstract
Background: Severe disease associated with respiratory syncytial virus (RSV) infection occurs predominantly among infants under 6 months of age. Vaccines for prevention are in clinical development. Assessment of the vaccine effectiveness in large epidemiological studies requires serological assays which are rapid, economical and standardised between laboratories. The objective of this study was to assess the agreement between two enzyme linked immunosorbent assays (ELISA) and the plaque reduction neutralisation test (PRNT) in quantifying RSV specific antibodies. Methods: Archived sera from 99 participants of the Kilifi Birth Cohort (KBC) study (conducted 2002-2007) were screened for RSV antibodies using 3 methods: ELISA using crude RSV lysate as antigen, a commercial RSV immunoglobulin G (IgG) ELISA kit from IBL International GmbH, and PRNT. Pearson correlation, Bland-Altman plots and regression methods were used in analysis. Results: There was high positive correlation between the IBL RSV IgG ELISA and PRNT antibodies (Pearson r=0.75), and moderate positive correlation between the crude RSV lysate IgG ELISA and PRNT antibodies (r= 0.61). Crude RSV lysate IgG ELISA showed a wider 95% limit of agreement (-1.866, 6.157) with PRNT compared to the IBL RSV IgG ELISA (1.392, 7.595). Mean PRNT titres were estimated within a width of 4.8 log 2PRNT and 5.6 log 2PRNT at 95% prediction interval by IBL RSV IgG and crude RSV lysate IgG ELISA, respectively. Conclusion: Although, the IBL RSV IgG ELISA is observed to provide a reasonable correlate for PRNT assay in detecting RSV specific antibodies, it does not provide an accurate prediction for neutralizing antibody levels. An RSV neutralising antibody level is likely to fall within 2.4 fold higher and 2.4 fold lower than the true value if IBL RSV IgG ELISA is used to replace PRNT assay. The utility of an ELISA assay in vaccine studies should be assessed independent of the PRNT method.
Highlights
Respiratory syncytial virus (RSV) is an important cause of annual epidemics of bronchiolitis and pneumonia in children less than five years of age worldwide[1,2,3,4,5]
To overcome the challenges experienced with plaque reduction neutralisation test (PRNT) as a technique for quantifying protective immunity correlates to respiratory syncytial virus (RSV) in large vaccine studies, we explored how well enzyme linked immunosorbent assays (ELISA) and PRNT methods agree in detecting levels of RSV specific antibodies, and in addition, investigated how accurate an ELISA method can predict the PRNT measurements and if it could be considered a suitable replacement for PRNT
Due to the moderate correlation observed in our study between PRNT and crude RSV lysate immunoglobulin G (IgG) ELISA, we suggest that, careful consideration should be made on the choice of ELISA based assays as a surrogate for a neutralization assay in epidemiological studies
Summary
Respiratory syncytial virus (RSV) is an important cause of annual epidemics of bronchiolitis and pneumonia in children less than five years of age worldwide[1,2,3,4,5]. The most severe disease occurs among infants under 6 months of age[6], making this group the principal target for RSV disease prevention. One approach showing particular promise is to protect the infant over the first few months of life by maternal vaccination. A maternal RSV vaccine which is based on a post-fusion F protein nanoparticle design[7], is undergoing phase 3 clinical trials (NCT02624947). The Fusion (F) protein in Novavax F nanoparticle vaccine is not a true post-fusion F protein vaccine. It is consistent with a prefusogenic form that is able to generate site-specific antibody responses to both the pre-fusion and post-fusion F conformations[1]
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