Background:
Understanding natural immunity in settings with high Streptococcus pyogenes burden is important for developing safe and effective vaccines.
Methods:
We performed a post-hoc investigation of participants enrolled in a randomised controlled trial of a live-attenuated influenza vaccine. S. pyogenes colonisation was determined with quantitative polymerase chain reaction (qPCR) to SpeB from nasopharyngeal swabs taken at baseline, day 7 and 21 amongst 201 children who received vaccination and 108 controls. Serum IgG to Cpa, M1, Mac, SpyAD and SpyCEP was quantified by ELISA.
Results:
Colonisation was detected in 71 children (22%) at any point in the study period. Only 19 (6%) were colonised on more than one occasion. 21/26 who were colonised at baseline were not colonised at day 7, and 13/23 were colonised at day 7 but not at day 21. Between vaccine and control groups, no significant difference in overall colonisation rates (23% vs 21%, p=0.8), incident colonisation (18 vs 11%, p=0.12), or qPCR-defined colonisation density was demonstrated. IgG titres to M1, SpyCEP, Mac, and SpyAD were significantly higher in colonised vs non-colonised controls (n=101, figure 1A). A significant rise in IgG was seen to M1 and SpyCEP following new colonisation between day 0 and 21(n=18, figure 1B).
Conclusion
S. pyogenes colonisation assessed by qPCR was prevalent, and frequently transient, over a 21-day period. Colonisation was associated with increased serum responses to S. pyogenes antigens. Further studies are needed to characterise the role of colonisation-induced natural immunity in the reduction of S. pyogenes disease incidence with age.
Figure 1: Serum IgG titres to S. pyogenes antigens