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Pneumococcal vaccines are a cornerstone for the prevention of pneumococcal diseases, reducing morbidity and mortality in children and adults worldwide. Pneumococcal vaccine composition is based on the polysaccharide capsule of Streptococcus pneumoniae, which is one of the most important identified contributors to the pathogen's virulence. Similarities in the structural composition of polysaccharides included in licensed pneumococcal vaccines may result in cross-reactivity of immune response against closely related serotypes, including serotypes not included in the vaccine. Therefore, it is important to understand whether cross-reactive antibodies offer clinical protection against pneumococcal disease. This review explores available evidence of cross-reactivity and cross-protection associated with pneumococcal vaccines, the challenges associated with the assessment of cross-reactivity and cross-protection, and implications for vaccine design and development. [ABSTRACT FROM AUTHOR]

Immune response elicited during pneumococcal carriage has been shown to protect against subsequent colonization and infection by Streptococcus pneumoniae. The study was designed to measure the baseline serotype-specific anti-capsular IgG concentration and opsonic titers elicited in response to asymptomatic carriage in adults with and without type 2-diabetes. Level of IgG to capsular polysaccharide was measured in a total of 176 samples (124 with type 2 diabetes and 52 without type 2 diabetes) against serotype 1, 19F, 9V, and 18C. From within 176 samples, a nested cohort of 39 samples was selected for measuring the functional capacity of antibodies by measuring opsonic titer to serotypes 19F, 9V, and 18C. Next, we measured levels of IgG to PspA in 90 samples from individuals with and without diabetes (22 non-diabetes and 68 diabetes). Our results demonstrated comparable IgG titers against all serotypes between those with and without type 2-diabetes. Overall, we observed higher opsonic titers in those without diabetes as compared to individuals with diabetes for serotypes 19F and 9V. The opsonic titers for 19F and 9V significantly negatively correlated with HbA1c. For 19F, 41.66% (n = 10) showed opsonic titers ≥ 1:8 in the diabetes group as compared to 66.66% (n = 10) in the non-diabetes group. The percentage was 29.6% (n = 7) vs 66.66% (n = 10) for 9V and 70.83% (n = 17) vs 80% (n = 12) for 18C in diabetes and non-diabetes groups respectively. A comparable anti-PspA IgG (p = 0.409) was observed in those with and without diabetes, indicating that response to protein antigen is likely to remain intact in those with diabetes. In conclusion, we demonstrated comparable IgG titers to both capsular polysaccharide and protein antigens in those with and without diabetes, however, the protective capacity of antibodies differed between the two groups. [ABSTRACT FROM AUTHOR]

BackgroundAlthough the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years.MethodsOne hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years.ResultsRelative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed.ConclusionsPCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points.Clinical trials registrationNCT00457977.

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