Abstract
ABSTRACTIndigenous populations experience high rates of otitis media (OM), with increased chronicity and severity, compared to those experienced by their nonindigenous counterparts. Data on immune responses to otopathogenic bacteria in these high-risk populations are lacking. Nontypeable Haemophilus influenzae (NTHi) is the predominant otopathogen in Australia. No vaccines are currently licensed to target NTHi; however, protein D (PD) from NTHi is included as a carrier protein in the 10-valent pneumococcal polysaccharide conjugate vaccine (PHiD10-CV), and other promising protein vaccine candidates exist, including outer membrane protein 4 (P4) and protein 6 (P6). We measured the levels of serum and salivary IgA and IgG against PD, P4, and P6 in Aboriginal and non-Aboriginal children with chronic OM who were undergoing surgery and compared the levels with those in healthy non-Aboriginal children (controls). We found that Aboriginal cases had lower serum IgG titers to all NTHi proteins assessed, particularly PD. In contrast, serum IgA and salivary IgA and IgG titers to each of these 3 proteins were equivalent to or higher than those in both non-Aboriginal cases and healthy controls. While serum antibody levels increased with age in healthy controls, no changes in titers were observed with age in non-Aboriginal cases, and a trend toward decreasing titers with age was observed in Aboriginal cases. This suggests that decreased serum IgG responses to NTHi outer membrane proteins may contribute to the development of chronic and severe OM in Australian Aboriginal children and other indigenous populations. These data are important for understanding the potential benefits of PHiD10-CV implementation and the development of NTHi protein-based vaccines for indigenous populations.
Highlights
Australian Aboriginal children experience an excessive burden of otitis media (OM) and associated hearing loss, which causes difficulties in language acquisition and learning and has long-term effects on their life course [1,2,3]
This was evident for protein D (PD), the carrier protein in PHiD10-CV, which is currently being assessed for its impact on OM in Australian Aboriginal children
Our data showed that Aboriginal children had approximately 25% of the serum IgG antibody responses to PD seen with healthy nonAboriginal children, suggesting that either hyporesponsiveness or the development of immune tolerance to PD may occur in this high-risk population
Summary
Australian Aboriginal children experience an excessive burden of otitis media (OM) and associated hearing loss, which causes difficulties in language acquisition and learning and has long-term effects on their life course [1,2,3]. We recently demonstrated that Australian Aboriginal children with OM produce similar antibody titers in response to conserved proteins of S. pneumoniae [20] This finding is in contrast to other studies that observed impaired antigen-specific immune responses to proteins from NTHi and S. pneumoniae [21,22,23,24,25]. Despite the almost universal nature of OM in Aboriginal communities and the predominance of NTHi disease, no studies have been conducted to assess the naturally acquired NTHi-specific antibodies in Aboriginal children These data are important to determine which surface-exposed proteins are immunogenic and/or appear to be protective, to help guide development of the best vaccine candidates for a broadly protective NTHi vaccine for Australian Aboriginal children. As both P4 and P6 are highly conserved and promising candidates that may be included in a multiprotein vaccine, it is impor-
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