Abstract
This study aimed to explore the feasibility of pneumococcal surface protein A (PspA) as a carrier protein. Three recombinant pneumococcal surface proteins from three different clades were expressed by the prokaryotic expression system and conjugated to group A meningococcal polysaccharide (GAMP) to generate three polysaccharide-protein conjugates. The conjugates, unconjugated proteins, GAMP, and GAMP-TT vaccine bulk (used as positive control) were immunized into mice, and their immune effects were assessed by the methods of enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), and serum bactericidal assay (SBA). The results showed that the polysaccharide-protein conjugates could produce higher levels of anti-GAMP IgG titers (P < 0.05), higher ratios of Th1/Th2 (P < 0.05), and higher levels of serum bactericidal activity (P < 0.05), compared with the unconjugated GAMP. The conjugation of PspAs to GAMP also enhanced the anti-PspA responses compared with unconjugated PspAs except for PspA3. In conclusion, the results indicated that the three PspAs were appropriate carrier proteins, as demonstrated by the characteristics of T-cell dependent responses to the GAMP, and might protect against group A of epidemic cerebrospinal meningitis.
Highlights
Polysaccharide encapsulated bacteria, such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, Neisseria meningitidis, and group B streptococcus, cause a major proportion of diseases in early childhood
pneumococcal surface protein A (PspA) was selected as a carrier protein of group A meningococcal polysaccharide (GAMP) conjugate to provide broad crossreactive protection against S. pneumoniae
The results showed that PspAs from both families 1 and 2 were appropriate as carrier proteins for preparing GAMP conjugates
Summary
Polysaccharide encapsulated bacteria, such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and group B streptococcus, cause a major proportion of diseases in early childhood. Capsular polysaccharide is a thymus independent antigen; immunization of infants and young children with this antigen does not induce high and long-lasting protective levels of serum antibodies. The success of the Hib conjugate vaccine highlighted the advantages of converting polysaccharides into T-dependent antigens by chemical conjugation to carrier proteins. A Gram-negative diplococcus known as the meningococcus, continues to be among the most important causes of bacterial meningitis worldwide.
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