Australian Aboriginal Children with Otitis Media Have Reduced Antibody Titers to Specific Nontypeable Haemophilus influenzae Vaccine Antigens

Abstract

Indigenous 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.

Serum antibody response to Moraxella catarrhalis proteins in stringently defined otitis prone children

“…[38][39][40] Moreover, they found that Australian aboriginal (possibly similar to OP) children with otitis media displayed lower serum IgG to NTHi but not Spn proteins than non-aboriginal (possibly similar to NOP) or healthy children. [41] Consistent with our findings, these observations also suggest that OP children in different geographic areas may have similar defects in producing serum antibodies to certain otopathogens. The full linear model is log 2 (Y i j ) = log 10 (A i j ) × COL i j × OP i + u i + e i j , i = 1, …, n, j = 1, …, n i , (1) where log 10 (A ij ) × COL ij × OP i includes all main effects and interactions, u i is a subject level random effect and e ij is the remaining error term.…”

PCV7- and PCV10-Vaccinated Otitis-Prone Children in New Zealand Have Similar Pneumococcal and Haemophilus influenzae Densities in Their Nasopharynx and Middle Ear

“…We have also observed that Aboriginal otitis-prone children have similar natural antibody titres to pneumococcal protein antigens when compared with their non-Aboriginal counterparts [39]. Aboriginal otitis-prone children did, however, have lower natural antibody titres to specific NTHi protein antigens [40], indicating that Aboriginal children may be tolerised to NTHi from a young age and cease responding to some NTHi antigens. It is possible that the different ethnic groups within the PCV10 group have different antibody responses to Protein D, but this had no impact on density of NTHi (or pneumococcal) colonisation.…”

Occurrence of and referral to specialists for pain-related diagnoses in First Nations and non–First Nations children and youth

“…These findings align with those of other research pertaining to Indigenous children's health showing high rates of dental conditions, inadequate access to dental care 5 and high rates of chronic ear infections. [40][41][42][43][44] Lower percentages of visits to ear-and throat-related specialists among the First Nations cohort compared with the non-First Nation cohort was an unexpected result considering the higher percentage of diagnoses for related conditions.…”