Nasopharyngeal Colonization Elicits Antibody Responses to Staphylococcal and Pneumococcal Proteins That Are Not Associated with a Reduced Risk of Subsequent Carriage

Abstract

Knowledge of the immunological correlates of Staphylococcus aureus and Streptococcus pneumoniae colonization is required for the search for future protein vaccines. We evaluated natural antibody levels against pneumococcal and staphylococcal proteins in relation to previous bacterial colonization with both pathogens. In a randomized controlled trial, nasopharyngeal samples were obtained from children at 1.5, 6, 12, 18, and 24 months and cultured for S. aureus and S. pneumoniae. Approximately 50% of the children were PCV7 vaccinated. Serum IgG against 18 pneumococcal and 40 staphylococcal proteins was semiquantified by Luminex technology from 111 12 month olds and 158 24 month olds. Previous culture-proven S. aureus colonization was associated with higher IgG levels against 6/40 staphylococcal proteins (ClfB, ClfA, Efb, CHIPS, LukD, and LukF [P < 0.001]) compared to noncarriers. Previous pneumococcal colonization was associated with increased IgG levels against 12/18 pneumococcal proteins compared to noncarriers (P < 0.003). Increasing age was associated with higher levels of antibodies to most pneumococcal proteins and lower levels of antibodies to over half the staphylococcal proteins, reflecting natural colonization dynamics. Anti-S. pneumoniae and anti-S. aureus protein antibodies at the age of 12 months were not negatively correlated with subsequent colonization with the homologous species in the following year and did not differ between PCV7-vaccinated and nonvaccinated children. Colonization with S. aureus and S. pneumoniae induces serum IgG against many proteins, predominantly proteins with immune-modulating functions, irrespective of PCV7 vaccination. None of them appeared to be protective against new acquisition with both pathogens, possibly due to the polymorphic nature of those proteins in the circulating bacterial population.

Effect of Pneumococcal Conjugate Vaccine on the Natural Antibodies and Antibody Responses Against Protein Antigens From Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Children With Community-acquired Pneumonia

“…Also, the antibody levels against cholinebinding protein A, pneumococcal choline-binding protein A and pneumococcal histidine triad protein D were lower in vaccinated children compared with unvaccinated controls, but this did not reach statistical significance. Similarly, in the study by Prevaes et al, 9 there was also a trend toward lower MFI readings in vaccinated children for the antigens Nan, Pilus A, PspA and PsaA in 24-month-old children. Conversely, Ditse et al 13 found no difference on the levels of antibodies against protein antigens between children vaccinated with PCV7 or unvaccinated.…”

“…[3][4][5] Few studies have addressed the development of natural antibodies and the frequency of antibody responses against protein antigens from S. pneumoniae, H. influenzae and M. catarrhalis. [9][10][11][12][13] In addition, most of these studies were conducted before the introduction of the current polysaccharide-based vaccines (PCV and H. influenzae type b vaccine), which does not represent the general pediatric population anymore. We aimed to evaluate differences in the levels of natural antibodies and in the frequencies of antibody responses associated with CAP against protein antigens from S. pneumoniae, H. influenzae and M. catarrhalis in children who had been vaccinated or left unvaccinated with 10-valent PCV (PCV10).…”

Staphylococcus aureusandStreptococcus pneumoniaeinteraction and response to pneumococcal vaccination: Myth or reality?

“…In addition, other studies did not find correlations between levels of particular S. aureus or S. pneumoniae antibodies and rates of S. aureus colonization. 67,68 S. pneumoniae pilus as a potential determinant in the interference mechanism…”

Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization

“…This antigenicity has been shown in both S. aureus-infected patients and healthy carriers (10,11). The exoproteins Hla, IsdB, IsaA, and ClfA elicit significantly higher levels of antibodies in patients than in healthy carriers.…”