Do antibodies to pneumococcal surface adhesin a prevent pneumococcal involvement in acute otitis media?

Antibodies to the pneumococcal (Pnc) surface protein PsaA are immunogenic and protective in experimental animal models, but their role in protection from Pnc disease in humans is not known. In the present study, the ability of antibodies to PsaA to prevent the progression of Pnc carriage to Pnc acute otitis media (Pnc AOM) was evaluated. Antibodies to PsaA were measured in acute-phase serum samples of children with AOM and with Streptococcus pneumoniae cultured from the nasopharynx. The risk of Pnc AOM was evaluated by a logistic regression model with anti-PsaA concentration as the predictive variable. Higher concentrations of antibodies to PsaA were associated with lower risk of the Pnc nasopharyngeal carriage progression to Pnc AOM. This was true in children 9-24 months old (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.31-0.78) but not in children <9 months old (OR, 0.81; 95% CI, 0.48-1.35).

Antibody response to the pneumococcal proteins pneumococcal surface adhesin A and pneumolysin in children with acute otitis media.

BACKGROUND: Pneumococcal surface adhesin A (PsaA) and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates, and they are immunogenic and protective against pneumococcal challenge in experimental animals. We have recently shown production of antibodies to PsaA and Ply in young children, but data on the immune response to these antigens during culture-confirmed pneumococcal infection are lacking. OBJECTIVES: To evaluate whether young children respond to S. pneumoniae by producing antibodies to PsaA and Ply during acute otitis media (AOM). SUBJECTS AND METHODS: A cohort of 329 children was followed prospectively from the age of 2 months to the age of 2 years. Paired sera were obtained during episodes of AOM and used to measure antibodies to PsaA and Ply by enzyme-linked immunosorbent assay. S. pneumoniae cultured from the middle ear fluid was taken as evidence of pneumococcal AOM. The presence of S. pneumoniae in the nasopharyngeal aspirate collected in connection of AOM or any other respiratory infection or in the nasopharyngeal swab collected at scheduled visits was taken to indicate pneumococcal carriage and thus a history of previous contact with S. pneumoniae. RESULTS: Children with previous pneumococcal contacts had high anti-PsaA and anti-Ply concentrations in the acute phase sera regardless of the nature (AOM or carriage) of the current pneumococcal contact. Of the children with no previous pneumococcal contact, those with current pneumococcal AOM had lower antibody concentrations than those with current pneumococcal carriage only. Anti-PsaA and anti-Ply responses were found in children with current pneumococcal contact. The antibody response was strongly associated with low acute phase antibody concentration, but not significantly with age and the nature of the current pneumococcal contact. CONCLUSIONS: We showed that infants are capable of developing a specific antibody response to the pneumococcal proteins PsaA and Ply during AOM.

Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media.

Pneumococcal surface protein A (PspA), pneumococcal surface adhesin A (PsaA), and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates. They are immunogenic and protective against pneumococcal challenge in animals and are the major candidates for a protein-based pneumococcal vaccine for humans. However, little is known of the natural development of antibodies to these proteins in humans. The objective of this study was to evaluate the natural development of antibodies to PspA, PsaA, and Ply in relation to pneumococcal infection and carriage in young children. Serum antibodies to these proteins were measured by EIA in children at ages 6, 12, 18, and 24 months and in their mothers. All age groups were capable of producing antibodies to the 3 proteins. The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media).

Human antibodies to pneumococcal surface protein A in health and disease.

BACKGROUND: Diseases caused by Streptococcus pneumoniae have a high impact in young children whose ability to mount antibodies to capsular polysaccharides is impaired. Pneumococcal surface protein A (PspA) is a potential vaccine candidate for this age group. METHODS: We used Western blot analysis and enzyme immunoassay to study human sera of healthy adults from Alabama (n = 20) and from Finland (n = 21), healthy children from Finland (n = 20) and ill children from Finland, those with pneumococcal invasive infection (n = 26) and those with nonpneumococcal invasive infection (n = 26). RESULTS: Human antibodies to PspA exhibited strong cross-reactivity among different pneumococcal strains. The geometric mean titer of IgG antibody to PspA in sera from 21 healthy adults was 4,040, from ten 3-year-old healthy children 1,080 and from ten 2-month-old healthy children 1,650. The geometric mean titer of PspA antibody of acute phase sera of children with invasive pneumococcal disease was 140, significantly (P < 0.001) lower than the respective value, 1,020, for children with infection caused by other bacteria. CONCLUSIONS: We demonstrate for the first time the existence of antibodies to PspA in human sera in health and disease. The findings in ill children suggest that antibodies to PspA might play a role in protection against pneumococcal disease.

Comparison of four different sampling methods for detecting pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children.

Samples from 96 children with acute respiratory infection were obtained simultaneously with nasal, nasopharyngeal, and oropharyngeal swabs and by nasopharyngeal aspiration and were cultured on chocolate and blood agar plates. The rates of isolation of Streptococcus pneumoniae and Haemophilus influenzae detected by the four sampling methods were compared. Nasopharyngeal aspirates were optimal for the detection of both S. pneumoniae (isolation rate, 33%) and H. influenzae (isolation rate, 31%). When a nasopharyngeal aspirate is not available, such as for healthy children or children with no obtainable secretions, the nasopharyngeal swab seems optimal for the detection of both S. pneumoniae and H. influenzae among children younger than 13 months of age. Among older children, similarly, the nasopharyngeal swab seems optimal for the detection of S. pneumoniae; however, for H. influenzae, the oropharyngeal swab seems optimal.

Pneumococcal capsular antigen detection after enrichment culture: an alternative to culture methods in epidemiologic research.

Bacterial culture of Streptococcus pneumoniae followed by serotyping is not always feasible under field conditions. Antigen detection methods could be an alternative, but they are associated with sensitivity problems. In an effort to improve their sensitivity, we introduced an enrichment phase before antigen detection and compared the results with direct bacterial culture, using nasopharyngeal swabs from 95 children with symptoms of acute respiratory infection. Antigen detection was performed by latex agglutination and counterimmunoelectrophoresis. Streptococcus pneumoniae was found in 29 (30%) of the samples by culture, and in 42 (44%) by antigen detection after enrichment, an excess of 45% over culture findings. This excess was shown to represent true positive samples since pneumococcal DNA could be detected by polymerase chain reaction in all 15 antigen-positive, culture-negative samples. Two culture-positive samples were antigen-negative; in one of these the bacteria were nonencapsulated. We conclude that for type-specific demonstration of S. pneumoniae, detection of pneumococcal antigen after an enrichment step is a sensitive method that can be applied for epidemiologic study purposes, e.g., in vaccine trials, in areas without ready access to a good microbiology laboratory.