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

View Article: PubMed Central - PubMed

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.

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Comparison of serum IgG (A), serum IgA (B), salivary IgG (C), and salivary IgA (D) antibody titers between healthy non-Aboriginal children, Aboriginal children with otitis media, and non-Aboriginal children with otitis media. Levels of serum IgG and IgA antibodies and salivary IgG and IgA antibodies against NTHi proteins are presented for each individual child, with the horizontal bars depicting the medians. Statistical analyses were conducted on the geometric means of logarithmically transformed data, correcting for age. □, healthy controls; ○, non-Aboriginal children with OM; ×, Aboriginal children with OM. P4, outer membrane protein 4; P6, outer membrane protein 6; PD, protein D. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.
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Figure 1: Comparison of serum IgG (A), serum IgA (B), salivary IgG (C), and salivary IgA (D) antibody titers between healthy non-Aboriginal children, Aboriginal children with otitis media, and non-Aboriginal children with otitis media. Levels of serum IgG and IgA antibodies and salivary IgG and IgA antibodies against NTHi proteins are presented for each individual child, with the horizontal bars depicting the medians. Statistical analyses were conducted on the geometric means of logarithmically transformed data, correcting for age. □, healthy controls; ○, non-Aboriginal children with OM; ×, Aboriginal children with OM. P4, outer membrane protein 4; P6, outer membrane protein 6; PD, protein D. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.

Mentions: Aboriginal children with OM had significantly lower serum IgG titers to P4, P6, and PD than did non-Aboriginal children with OM or healthy controls (P ≤ 0.004) (Fig. 1A). Anti-PD serum IgG titers were significantly lower in both Aboriginal and non-Aboriginal children with OM than in healthy controls (P ≤ 0.003) and were also lower in Aboriginal children with OM than in non-Aboriginal children with OM (P = 0.002) (Fig. 1A). Anti-P4 serum IgG titers were significantly lower in Aboriginal children with OM than in non-Aboriginal children with OM (P ≤ 0.0001) and healthy controls (P ≤ 0.0001). Anti-P6 serum IgG titers were significantly lower in Aboriginal children with OM than in healthy controls (P = 0.042). Conversely anti-P6 serum IgA titers were significantly higher in Aboriginal children with OM than in healthy controls (P = 0.001) (Fig. 1B). Anti-P4 and anti-PD serum IgA titers were similar among the groups.


Australian Aboriginal Children with Otitis Media Have Reduced Antibody Titers to Specific Nontypeable Haemophilus influenzae Vaccine Antigens
Comparison of serum IgG (A), serum IgA (B), salivary IgG (C), and salivary IgA (D) antibody titers between healthy non-Aboriginal children, Aboriginal children with otitis media, and non-Aboriginal children with otitis media. Levels of serum IgG and IgA antibodies and salivary IgG and IgA antibodies against NTHi proteins are presented for each individual child, with the horizontal bars depicting the medians. Statistical analyses were conducted on the geometric means of logarithmically transformed data, correcting for age. □, healthy controls; ○, non-Aboriginal children with OM; ×, Aboriginal children with OM. P4, outer membrane protein 4; P6, outer membrane protein 6; PD, protein D. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5382827&req=5

Figure 1: Comparison of serum IgG (A), serum IgA (B), salivary IgG (C), and salivary IgA (D) antibody titers between healthy non-Aboriginal children, Aboriginal children with otitis media, and non-Aboriginal children with otitis media. Levels of serum IgG and IgA antibodies and salivary IgG and IgA antibodies against NTHi proteins are presented for each individual child, with the horizontal bars depicting the medians. Statistical analyses were conducted on the geometric means of logarithmically transformed data, correcting for age. □, healthy controls; ○, non-Aboriginal children with OM; ×, Aboriginal children with OM. P4, outer membrane protein 4; P6, outer membrane protein 6; PD, protein D. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.
Mentions: Aboriginal children with OM had significantly lower serum IgG titers to P4, P6, and PD than did non-Aboriginal children with OM or healthy controls (P ≤ 0.004) (Fig. 1A). Anti-PD serum IgG titers were significantly lower in both Aboriginal and non-Aboriginal children with OM than in healthy controls (P ≤ 0.003) and were also lower in Aboriginal children with OM than in non-Aboriginal children with OM (P = 0.002) (Fig. 1A). Anti-P4 serum IgG titers were significantly lower in Aboriginal children with OM than in non-Aboriginal children with OM (P ≤ 0.0001) and healthy controls (P ≤ 0.0001). Anti-P6 serum IgG titers were significantly lower in Aboriginal children with OM than in healthy controls (P = 0.042). Conversely anti-P6 serum IgA titers were significantly higher in Aboriginal children with OM than in healthy controls (P = 0.001) (Fig. 1B). Anti-P4 and anti-PD serum IgA titers were similar among the groups.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus