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Immunologic epitope, gene, and immunity involved in pneumococcal glycoconjugate
1Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852-1448, USA.
Insights
Monoclonal antibodies targeting pneumococcal polysaccharide showed reduced binding after O-acetyl removal, but still offered protection against infection. This suggests potential for improved conjugate vaccines in young children.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Pneumococcal infections cause significant infant morbidity and mortality, particularly pneumonia, otitis media, and meningitis.
- Children under two years old exhibit the highest incidence rates of pneumococcal diseases.
- Current vaccines face challenges with immunogenicity in young children.
Purpose of the Study:
- To investigate the production and binding characteristics of monoclonal antibodies (MAbs) against pneumococcal polysaccharide (PS).
- To evaluate the protective efficacy of a type 9V IgG MAb against pneumococcal infection.
- To explore the potential of protein antigens as components or carriers for pneumococcal conjugate vaccines.
Main Methods:
- Production of monoclonal antibodies (MAbs) targeting pneumococcal polysaccharide (PS).
- Assessment of MAb binding characteristics to PS epitopes, including the effect of O-acetyl group removal.
- Evaluation of passive protection and enhancement of opsonophagocytic activity by type 9V IgG MAb.
Main Results:
- Alkali hydrolysis removal of O-acetyl groups from 9V PS decreased binding with rabbit antiserum but had less impact on 9V MAb binding.
- Type 9V IgG MAb conferred passive protection against pneumococcal infection.
- The MAb enhanced polymorphonuclear (PMN) leukocyte activity, improving the killing of type 9V pneumococci.
Conclusions:
- Monoclonal antibody binding to pneumococcal polysaccharide is relatively stable despite O-acetyl group modifications.
- Type 9V IgG MAb demonstrates protective capabilities and enhances immune cell function against pneumococcal pathogens.
- Glycoconjugate vaccines, linking PS to protein carriers, offer a promising strategy to improve vaccine efficacy in young children.
Abstract:
Pneumococcal infection persists as a major cause of pneumonia, otitis media, and meningitis in infants. Children less than 2 years of age show the highest incidence of pneumococcal diseases. Production of monoclonal antibody (MAb) to polysaccharide (PS) and binding characteristics to PS epitopes were studied. Removal of the O-acetyl group from 9V PS by alkali hydrolysis resulted in a decreased binding with rabbit 9V antiserum (AS). However, the binding reaction with 9V MAb was less affected by the loss of O-acetyl content. Type 9V IgG MAb provided passive protection and enhanced the opsonophagocytic activity of polymorphonuclear (PMN) leukocytes to kill type 9V pneumococci. The pathogenecity of pneumococci is attributed to various virulence factors distributed on the cell surface, including capsular polysaccharide and protein antigens, for example, pneumolysin, autolysin, pneumococcal surface protein A (PspA), pneumococcal surface adhesion (PsaA), and hemin binding protein. Some of these protein antigens may be used as a component to combine with pneumococcal PS vaccine or as a carrier of conjugate vaccine. Clinical trials of pneumococcal conjugate vaccines showed that covalent linkage of capsular PS to protein carriers improved the immunogenicity of the PS. Development of glycoconjugate vaccine for selected pneumococcal types will help solve the problem of poor immunogenecity of PS vaccine in young children used for prevention of pneumococcal infection.