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Immunologic priming of young children by pneumococcal glycoprotein conjugate, but not polysaccharide, vaccines
K L O'Brien1, M C Steinhoff, K Edwards
1Department of International Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Insights
Pneumococcal glycoprotein conjugate vaccines prime children for stronger antibody responses to later polysaccharide vaccines. This suggests the conjugate vaccines induce a T cell-dependent immune response, crucial for effective immunization against pneumococcal disease.
Area of Science:
- Immunology
- Vaccinology
- Pediatrics
Background:
- Streptococcus pneumoniae causes significant invasive bacterial disease and otitis media in young children.
- Current pneumococcal polysaccharide vaccines lack reliable immunogenicity in children under two.
- Pneumococcal glycoprotein conjugate vaccines are under evaluation for pediatric use.
Purpose of the Study:
- To evaluate the immunogenicity and priming capacity of a bivalent pneumococcal glycoprotein conjugate vaccine (serotypes 6A and 23F) in children.
- To assess the kinetics of pneumococcal IgG antibody response following primary immunization.
- To determine the effect of secondary immunization on antibody response and IgG subclass distribution.
Main Methods:
- 60 children aged 18–30 months received one dose of bivalent pneumococcal polysaccharide-CRM197 vaccine.
- A subgroup of 20 children received a secondary immunization with pneumococcal polysaccharide vaccine (serotypes 6B and 23F) 11–20 months later.
- Pneumococcal IgG antibody concentrations and IgG subclass distributions were analyzed.
Main Results:
- Pneumococcal IgG antibody concentrations remained stable for 12 months post-primary immunization.
- Secondary immunization with polysaccharide vaccine induced a significantly greater anamnestic response in children previously primed with glycoprotein conjugate vaccine compared to polysaccharide-primed children.
- A stronger IgG response was observed for serotype 23F than for 6B.
- Primary immunization elicited primarily IgG1 antibodies, while secondary immunization induced both IgG1 and IgG2 subclasses.
Conclusions:
- Pneumococcal glycoprotein conjugate vaccines effectively prime for enhanced anamnestic IgG antibody responses to subsequent polysaccharide immunization.
- The vaccine likely induces a T cell-dependent immune response, beneficial for long-term immunity.
- Pneumococcal serotype influences vaccine immunogenicity, with serotype 23F showing a greater response than 6B.
Background:
Streptococcus pneumoniae is the most common cause of invasive bacterial disease and otitis media in infants and young children. Licensed pneumococcal polysaccharide vaccines are not reliably immunogenic in children younger than 2 years of age; therefore pneumococcal glycoprotein conjugate vaccines are currently being evaluated for safety, immunogenicity and efficacy in various age groups.
Methods:
During a 12-month period we determined the kinetics of pneumococcal IgG antibody in 60 children who received primary immunization with one dose of bivalent (serotypes 6A and 23F) pneumococcal polysaccharide-CRM197 vaccines at 18 to 30 months of age. To assess immunologic priming a subgroup of 20 subjects received secondary immunization with pneumococcal polysaccharide vaccine, including serotypes 6B and 23F, at 11 to 20 months after primary immunization. Pneumococcal-specific IgG subclass distributions were also evaluated in the subgroup.
Results:
In the 12 months after primary immunization with glycoprotein conjugate vaccine, geometric mean pneumococcal IgG antibody concentrations to 6B and 23F serotypes remained stable. Pneumococcal polysaccharide vaccine induced a greater anamnestic response in children primed with glycoprotein conjugate vaccines (13- to 40-fold increases to geometric mean concentrations of 6 to 30 micrograms/ml for type 23F), than in those primed with polysaccharide (2- to 4-fold increases). A greater IgG response to pneumococcal serotype 23F than to 6B was observed with both primary and secondary immunization. The serotype-specific pneumococcal IgG antibody response was virtually restricted to the IgG1 subclass after primary immunization, but secondary immunization elicited antibodies of IgG1 and IgG2 subclasses.
Conclusions:
These glycoprotein conjugate vaccines appear to prime for anamnestic IgG antibody responses to subsequent immunization with polysaccharide vaccine, suggesting that the polysaccharide-CRM197 vaccine effectively induces a predominantly T cell-dependent immune response. The greater IgG response to 23F than to 6B indicates that pneumococcal serotype is a major determinant of immunogenicity of pneumococcal glycoprotein conjugate vaccines.