Otitis media (OM) or middle ear infections are common in young children. Children who develop recurrent/chronic infections are considered otitis prone (OP). Australian Aboriginal children are disproportionately affected by OM with chronic disease almost universal in remote communities. It is thought children in these remote areas experience more of the common risk factors associated with enhanced exposure to the major OM pathogen, non-typeable Haemophilus influenzae (NTHi). NTHi protein-based vaccines including antigens important for infection and persistence (rsPilA, ChimV4 and Protein D) are under development. We hypothesised that antibodies against these antigens would be reduced in OP children, particularly Aboriginal children living in remote areas.
Serum was collected from Aboriginal cases (n=77), non-Aboriginal cases (n=70) and non-Aboriginal healthy controls (n=36). Naturally acquired serum IgG titres to NTHi antigens; rsPilA, ChimV4, Protein D and OMP26, were measured using an in-house multiplex fluorescent bead immunoassay. IgG geometric mean concentrations (GMCs) were adjusted for age and compared between groups using an univariate analysis model.
Aboriginal cases had lower IgG to rsPilA, ChimV4 and Protein D (GMC: 88.94, 429.66 and 194.81AU/mL respectively) compared to non-Aboriginal cases (GMC: 240.57, 1210.76 and 493.24AU/mL respectively), and controls (227.69, 872.18 and 509.28AU/mL respectively; p<0.05). IgG to these antigens were similar between Aboriginal cases from remote (n=38) and metropolitan (n=31) Western Australia (WA) (GMCs: rsPilA= 93.60 vs 83.10AU/mL; ChimV4= 460.62 vs 392.68AU/mL and PD= 203.77 vs 183.83AU/mL). IgG to OMP26 was similar between cases and controls (GMC: Aboriginal cases 1060AU/mL, non-Aboriginal cases 1054AU/mL and controls 820.2AU/mL). However, IgG to OMP26 was two-fold higher in Aboriginal cases from remote compared to those from metropolitan WA (GMCs: 1237.69 vs 643.55AU/mL; p<0.05).
Lower IgG to NTHi vaccine candidates in Aboriginal children suggests a failure to develop antibodies in response to NTHi exposure. While this was similar in Aboriginal children from remote and metropolitan areas, differences in IgG titres to OMP26 in Aboriginal children based on remoteness suggests OMP26 may be a marker of exposure. Importantly, our data suggest that the impact of OM may be reduced in all Aboriginal children by boosting their antibody titres with an NTHi vaccine containing these candidate antigens.