10.1 Mechanism of Action
S. pneumoniae (pneumococcus) is a gram-positive diplococcus that can cause invasive disease including meningitis, sepsis, and pneumonia with bacteremia and non-invasive disease such as pneumonia without bacteremia. Non-bacteremic pneumococcal pneumonia accounts for the majority of pneumococcal disease cases among the adult population. Over 100 different serotypes of pneumococcus have been identified. The serotypes included in PREVNAR 20 were selected based on their relevance in causing global disease and have been associated with higher case fatality rates and mortality, antibiotic resistance, meningitis and outbreaks.
PREVNAR 20 contains 20 pneumococcal capsular polysaccharides all conjugated to CRM197 carrier protein, which modifies the immune response to the polysaccharide from a T cell independent response to a T cell dependent response. The T-cell dependent response leads to a higher antibody response, and induces antibodies that enhance opsonisation, phagocytosis and killing of pneumococci to protect against pneumococcal disease, as well as generation of memory B cells, allowing for an anamnestic (booster) response on re-exposure to bacterial polysaccharide. In the absence of T-cell help, plain polysaccharide (PS) stimulated B-cells predominantly produce IgM antibodies; there is generally no affinity maturation of the antibodies, and no memory B-cells are generated. As vaccines, PSs are associated with poor or absent immunogenicity in infants less than 24 months of age and failure to induce immunological memory at any age.
Immune responses in children and adults following natural exposure to S. pneumoniae or following pneumococcal vaccination can be determined by measuring opsonophagocytic activity (OPA) and immunoglobulin G (IgG) responses. OPA represents functional antibodies and is considered an important immunologic surrogate measure of protection against pneumococcal disease in adults. In children, multiple immunogenicity criteria are used for the clinical evaluation of pneumococcal conjugate vaccines including the IgG antibody level of 0.35 mcg/mL using the World Health Organization (WHO) enzyme linked immunosorbent assay (ELISA) or equivalent assay-specific value.The levels of circulating antibodies in adults and the serotype-specific IgG levels in pediatric populations that correlate with protection against pneumococcal disease have not been clearly defined.
10.4 Burden of Disease
Disease Burden for Infants and Children
Despite reductions in disease due to PREVNAR (7vPnC) and PREVNAR 13 (13vPnC), a significant burden of pediatric pneumococcal disease remains in Canada, with a substantial portion caused by the 7 additional serotypes found in PREVNAR 20, including serotypes 8, 10A, 11A, 12F and 15B that are unique to PREVNAR 20. The incidence of pneumococcal disease in children is age specific, with the highest incidence among children <5 years of age (particularly among those <2 years of age). Although the incidence of pneumococcal disease is lower in older children and adolescents than in younger children, healthy older children and adolescents still have some risk of pneumococcal disease. Incidence, severity, and case fatality rates are significantly elevated among older children with risk factors for pneumococcal disease, such as chronic medical conditions (including heart, kidney, liver or lung disease; diabetes, neurologic conditions, cerebrospinal fluid leak, asthma, cochlear implants), and particularly among children with immunosuppression or immunodeficiencies (including HIV infection, HSCT, SCD, cancer, congenital immunodeficiencies, nephrotic syndrome and receipt of immunocompromising therapy).