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Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions
R S Daum1, D Hogerman, M B Rennels
1Department of Pediatrics, University of Chicago, Illinois, USA.
Insights
Polysaccharide (PS) pneumococcal conjugate vaccines (Pn-CRM197) are more immunogenic than oligosaccharide (OS) versions in infants. Higher PS doses showed a dose-response, suggesting optimized vaccine formulations for better protection.
Area of Science:
- Immunology
- Vaccinology
- Pediatric Infectious Diseases
Background:
- Pneumococcal conjugate vaccines (PCVs) are crucial for preventing invasive pneumococcal disease.
- Evaluating different formulations of pentavalent pneumococcal conjugate vaccines (Pn-CRM197) is essential for optimizing infant immunization strategies.
Purpose of the Study:
- To compare the immunogenicity and safety of Pn-CRM197 vaccines with varying saccharide chain lengths (oligosaccharide [OS] vs. polysaccharide [PS]) and quantities (0.5, 2, or 5 microg).
- To assess the impact of Pn-CRM197 on the immunogenicity of co-administered Haemophilus type b oligosaccharide conjugate (HbOC) vaccine.
Main Methods:
- A randomized controlled trial involving 400 infants immunized at 2, 4, and 6 months of age.
- Evaluation of six Pn-CRM197 formulations differing in saccharide type and dose.
- Measurement of antibody concentrations against five capsular serotypes and anti-PRP antibodies.
Main Results:
- All Pn-CRM197 vaccines were well-tolerated and elicited higher antibody concentrations than controls.
- Polysaccharide (PS) formulations demonstrated greater immunogenicity compared to oligosaccharide (OS) counterparts.
- A significant dose-response was observed for PS vaccines (5 microg > 2 microg > 0.5 microg), with minimal difference between 5 and 2 microg doses.
- Mean anti-PRP antibody concentrations were significantly higher in Pn-CRM197 recipients.
Conclusions:
- Pneumococcal conjugate vaccines utilizing polysaccharide (PS) antigens are more immunogenic than those using oligosaccharide (OS) antigens.
- The findings suggest that a reduced dose of Haemophilus type b oligosaccharide conjugate (HbOC) vaccine may be sufficient when co-administered with Pn-CRM197, due to enhanced immunogenicity.
Abstract:
Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among 400 infants. The vaccines differed in saccharide chain length (oligosaccharide [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg). Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls) for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and elicited mean antibody concentrations that exceeded those in controls for all 5 capsular serotypes. PS formulations were generally more immunogenic than their OS counterparts. For PS vaccines, a dose-response was documented (5 microg > 2 microg > 0.5 microg), but the differences between the 5- and 2-microg formulations were insignificant. The mean anti-PRP antibody concentration was significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines are more immunogenic than OS vaccines. The improved immunogenicity from Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn-CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit protection.