Salivary antibodies induced by the seven-valent PncOMPC conjugate vaccine in the Finnish Otitis Media Vaccine Trial.

BACKGROUND: Mucosal antibodies have been suggested to have a role in defence against pneumococcal infections. We investigated here the ability of a seven-valent pneumococcal conjugate vaccine, PncOMPC, to induce mucosal immune response. METHODS: Healthy Finnish children (n = 111), a subcohort of the Finnish Otitis Media Vaccine Trial, were recruited and 56 of them were immunised with the PncOMPC at the age of 2, 4, and 6 months. At 12 months of age, 49 of them received the PncOMPC and 7 were vaccinated with the pneumococcal polysaccharide vaccine (PncPS) as a booster. The control group of 55 children received a hepatitis B vaccine at the same ages. Salivary anti-Pnc IgG, IgA, IgA1, and IgA2 antibodies to serotypes 6B, 14, 19F, and 23F were measured in both groups at the age of 7 and 13 months. RESULTS: Salivary anti-Pnc IgG and IgA were detected more often in the PncOMPC than in the control group. However, the difference between groups was significant only for 19F and 23F IgA concentrations at the age of 7 months. At the age of 13 months, antibody concentrations did not differ between PncOMPC and control groups. The rises in IgA concentrations between 7 and 13 months of age were mainly of subclass IgA1. Further, there is a clear trend that PncPS booster induces higher salivary anti-Pnc PS antibody concentrations than the PncOMPC. CONCLUSION: We found that PncOMPC can induce a mucosal IgA response. However, the actual impact of mucosal antibodies in protection against pneumococcal infections is not clear.

Immunogenicity and safety of the eleven valent pneumococcal polysaccharide-protein D conjugate vaccine in infants.

BACKGROUND: Development is ongoing to increase the serotype coverage of pneumococcal conjugate vaccines. We report here the immunogenicity and safety of a new 11-valent pneumococcal conjugate vaccine (Pn-PD) in infants. METHODS: In a randomized, single blind study, 154 Finnish infants received 1 of 3 regimens: 4 doses of Pn-PD at 2, 4, 6 and 12-15 months; 3 doses of the Pn-PD at 2, 4 and 6 months and 1 dose of 23-valent polysaccharide vaccine (PncPS) at 12-15 months; or 3 doses of the hepatitis B vaccine at 2, 4 and 6 months and Pn-PD at 12-15 months. Serum IgG antibodies to vaccine serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F were measured with an enzyme immunoassay at the ages of 2, 7 and 12-15 months and at 4 or 28 days after the last vaccination. Local and systemic reactions were recorded by parents during 8 days after each dose. Serious adverse reactions were recorded during the entire study period. RESULTS: There was a significant increase in the IgG concentrations to vaccine serotypes after 3 doses of Pn-PD. Antibody concentrations after the primary series varied between 1.26 and 4.92 microg/ml depending on the serotype and study group. PncPS vaccine induced a better booster response than the Pn-PD, measured at 28 days after the fourth dose. IgG concentrations after the Pn-PD booster ranged between 1.60 and 9.63 microg/ml and after the PncPS booster between 4.24 and 40.54 microg/ml, depending on the serotype. The antibody concentrations after the first dose of Pn-PD administered at 12-15 months increased significantly but were lower than after the fourth dose at the same age. No significant antibody increase was measured 4 days after the vaccinations at 12-15 months. The safety profile of the vaccine was acceptable. CONCLUSIONS: The Pn-PD we tested was immunogenic and safe in infants.

Serum IgM antibodies contribute to high levels of opsonophagocytic activities in toddlers immunized with a single dose of the 9-valent pneumococcal conjugate vaccine.

In immunogenicity trials of pneumococcal conjugate vaccines (PCVs), only IgG antibody concentrations to pneumococcal capsular polysaccharides (PPSs) are usually determined, along with the opsonophagocytic activity (OPA) of antipneumococcal antibodies. We aimed to determine the role of both IgG and IgM in OPA in toddlers receiving one dose of 9-valent PCV (PCV9). The IgG and IgM antibody concentrations to PPSs of serotypes 6A, 9V, 14, 19F, and 23F were measured by enzyme immunoassay in sera from toddlers (ages 18 to 35 months) 1 month after a single PCV9 dose. The OPA for the same serotypes was measured by multiplexed opsonophagocytosis assay (MOPA). Further, IgG and IgM concentrations and MOPA were measured to PPS of serotypes 6A, 14, and 19F in sera collected 12 months after vaccination. The detected MOPA titers were high in comparison to the IgG concentrations 1 month after immunization. The IgM concentrations were higher than IgG concentrations for serotypes 6A and 14 (P < 0.001) and as high as IgG for serotypes 9V, 19F, and 23F. Correlation of the IgM antibody concentrations with MOPA (r = 0.35 to 0.65) was stronger compared to that of the IgG antibodies (r = 0.07 to 0.41). The depletion of IgG antibodies in three sets of pooled sera only slightly decreased the OPA activity against serotype 14. At 12 months after immunization, 50 to 100% of serum samples still showed detectable MOPA activity against serotypes 6A, 14, and 19F. Our results suggest that IgM contributes to OPA 1 month after a single PCV9 vaccination in toddlers and that functionally active IgM and IgG antibodies persist for at least a year.

Association of serotype-specific antibody concentrations and functional antibody titers with subsequent pneumococcal carriage in toddlers immunized with a 9-valent pneumococcal conjugate vaccine.

Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti-serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage.

Impact of the conjugation method on the immunogenicity of Streptococcus pneumoniae serotype 19F polysaccharide in conjugate vaccines.

7vCRM (Pfizer, Inc.) and PHiD-CV (GlaxoSmithKline Biologicals) are two pneumococcal conjugate vaccines licensed for the prevention of invasive pneumococcal disease and acute otitis media caused by the vaccine serotypes of Streptococcus pneumoniae. Neither vaccine contains serotype 19A, but both contain the closely related serotype 19F. No decrease in the incidence of serotype 19A disease has been observed following the introduction of 7vCRM, suggesting that this serotype 19F-containing vaccine provides limited cross-protection against serotype 19A. To investigate the impact that conjugation methods may have on antipolysaccharide immune responses and to determine whether this limited cross-protection is characteristic of the serotype 19F polysaccharide or rather of the 19F-CRM (cross-reacting material) conjugate, we compared naturally induced antibodies against serotypes 19F and 19A with antibodies induced after vaccination with different pneumococcal conjugate vaccines. We found that conjugation of the serotype 19F polysaccharide using reductive amination (as in 7vCRM) resulted in the formation of at least one additional epitope that is not present in the native form of the 19F polysaccharide or following 19F conjugation using a bifunctional spacer (as in the prototype vaccine 7vOMPC) or cyanylation (as in PHiD-CV). We also found that pneumococcal vaccines conjugated using cyanylation induce more opsonophagocytic antibodies against serotype 19F and a considerably higher level of cross-opsonophagocytic antibodies against serotype 19A than vaccines conjugated using reductive amination. In conclusion, these results suggest that the conjugation method can influence the functionality of the antibodies induced against the homologous serotype 19F and the cross-reactive serotype 19A of S. pneumoniae.

Salivary antibodies induced by the seven-valent PncCRM conjugate vaccine in the Finnish Otitis Media Vaccine Trial.

We studied salivary antibodies induced by a seven-valent pneumococcal conjugate vaccine (PncCRM). Healthy Finnish children (n=115), a subcohort of the Finnish Otitis Media (FinOM) Vaccine Trial, were immunised either with the PncCRM or a control vaccine (hepatitis B) at the age of 2, 4, 6, and 12 months. Salivary IgG, IgA, IgA1, IgA2 and sIg for serotypes 6B, 14, 19F, and 23F were measured at 7 and 13 months of age, and IgG and IgA also at 4-5 years of age. The PncCRM could induce both salivary anti-Pnc polysaccharide IgG and IgA. However, by the age of 4-5 years IgA concentrations had increased in both groups and were similar. The increases in IgA concentrations were mostly of IgA1 subclass. The difference between the PncCRM and the control group was more notable for serotypes 6B, 14 and 23F than for serotype 19F. We could not find evidence for the development of mucosal immunologic memory after vaccination with the PncCRM.