Salivary Immune Responses to the 7-Valent Pneumococcal Conjugate Vaccine in the First 2 Years of Life

Abstract

BackgroundThe CRM197-conjugated 7-valent pneumococcal vaccine (PCV7) is protective against vaccine serotype disease and nasopharyngeal carriage. Data on PCV7-induced mucosal antibodies in relation to systemic or natural anticapsular antibodies are scarce.MethodsIn a randomized controlled setting, children received PCV7 at age 2 and 4 months (2-dose group), at age 2, 4 and 11 months (2+1-dose group) or no PCV7 (control group). From 188 children paired saliva samples were collected at 12 and 24 months of age. From a subgroup of 15 immunized children also serum samples were collected. IgG and IgA antibody-levels were measured by multiplex immunoassay.ResultsAt 12 months, both vaccine groups showed higher serum and saliva IgG-levels against vaccine serotypes compared with controls which sustained until 24 months for most serotypes. Salivary IgG-levels were 10–20-fold lower compared to serum IgG, however, serum and saliva IgG-levels were highly correlated. Serum and salivary IgA-levels were higher in both vaccine groups at 12 months compared with controls, except for serotype 19F. Higher salivary IgA levels remained present for most serotypes in the 2+1-dose group until 24 months, but not in the 2-dose group. Salivary IgA more than IgG, increased after documented carriage of serotypes 6B, 19F and 23F In contrast to IgG, salivary IgA-levels were comparable with serum, suggesting local IgA-production.ConclusionsPCV7 vaccination results in significant increases in salivary IgG and IgA-levels, which are more pronounced for IgG when compared to controls. In contrast, salivary anticapsular IgA-levels seemed to respond more to natural boosting. Salivary IgG and IgA-levels correlate well with systemic antibodies, suggesting saliva might be useful as potential future surveillance tool.

Pneumococcal conjugate vaccine primes mucosal immune responses to pneumococcal polysaccharide vaccine booster in Papua New Guinean children

“…In line with a study conducted in the Netherlands, we found that serum and saliva IgG antibodies were correlated after booster vaccination [21] . Whereas it is likely that the IgG antibodies present at moderate levels in saliva after primary PCV immunization and at higher levels after PPV booster vaccination diffused from serum, some IgG may have been produced in the upper respiratory mucosa.…”

“…Possibly this early colonization stimulates the development of mucosal vaccine responses, unlike systemic vaccine responses that reportedly may be suppressed in individuals colonized with vaccine serotypes before vaccination [34] , [35] . Findings are more consistent for responses after booster vaccination with studies from the UK, Finland and the Netherlands reporting that PCV-serotype-specific salivary IgA and IgG responses are increased in PCV-primed children after booster vaccination with PPV or PCV [19] , [21] , [33] . In line with these studies in low-risk children, we have demonstrated that PCV primes for immune memory responses that result in enhanced mucosal IgA and IgG antibody responses to subsequent booster vaccination even when PCV is given at very young age.…”

“…Pneumococcal conjugate vaccines (PCVs) induce systemic immune responses that are highly effective in preventing IPD due to vaccine serotypes in children in both low- and high-risk settings [15] , [16] . In low-endemicity settings PCVs also reduce vaccine-serotype-specific carriage and mucosal infections [17] , [18] and specific IgA and IgG antibodies can be detected in saliva of children who have completed their primary PCV immunizations, although levels vary between vaccine serotypes and between children [19] , [20] , [21] . Subsequent booster vaccination with pneumococcal polysaccharide vaccine (PPV) or PCV was shown to increase salivary IgA responses for PCV serotypes, which has led to the suggestion that primary PCV vaccination induces mucosal immune memory [19] , [20] , [21] .…”

Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

“…This is probably due to the mechanism of mucosal transportation; which is known to be passive for IgG (high blood concentration is required) and active for IgA. In addition, covalently conjugated polysaccharide vaccines, applied parenterally, contribute to the control of the infection by indirect protection by reducing the carriage rates ( 35 ) and herd immunity ( 36 , 37 ), but salivary anticapsular IgA-levels seem to respond much better to natural boosting ( 38 ). Nevertheless, the influence of carriage over immunization is not clear.…”

Development and Evaluation of a Multiplex Microsphere Assay for Quantitation of IgG and IgA Antibodies against Neisseria meningitidis Serogroup A, C, W, and Y Polysaccharides

“…Polysaccharides need a coupling molecule and, thus, an additional step for conjugating them onto the microspheres. Several methods for conjugation to microspheres have been developed using polysaccharides from different bacterial species (6,8,9,(11)(12)(13)(14)(15). A comparative study of different coupling agents showed that the nontoxic 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) was the overall preferred coupling agent when conjugating pneumococcal polysaccharides to microspheres (15).…”