Adjuvant system AS02V enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: randomised, controlled trials.

Background: The protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD).

Objective: To evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02V) in older (≥65 years) and young (18-45 years) healthy adults.

Multilaboratory comparison of Streptococcus pneumoniae opsonophagocytic killing assays and their level of agreement for the determination of functional antibody activity in human reference sera.

Antibody-mediated killing of Streptococcus pneumoniae (pneumococcus) by phagocytes is an important mechanism of protection of the human host against pneumococcal infections. Measurement of opsonophagocytic antibodies by use of a standardized opsonophagocytic assay (OPA) is important for the evaluation of candidate vaccines and required for the licensure of new pneumococcal conjugate vaccine formulations. We assessed agreement among six laboratories that used their own optimized OPAs on a panel of 16 human reference sera for 13 pneumococcal serotypes.

Evaluation of pneumococcal polysaccharide immunoassays using a 22F adsorption step with serum samples from infants vaccinated with conjugate vaccines.

The history of the pneumococcal polysaccharide enzyme-linked immunosorbent assay (ELISA) is characterized by a continuous search for increased specificity. A third-generation ELISA that uses 22F polysaccharide inhibition has increased the specificity of the assay, particularly at low antibody concentrations. The present work compared various 22F ELISAs and non-22F ELISAs.

Pneumococcal carriage and acute otitis media induce serum antibodies to pneumococcal surface proteins CbpA and PhtD in children.

We assessed the development and role of serum anti-CbpA and -PhtD in early childhood in relation to pneumococcal exposure. Serum IgG concentrations to CbpA and PhtD were measured with enzyme immunoassay in serum samples collected at the ages of 6, 12, 18, and 24 months from 50 healthy children and from 50 adults. Furthermore, antibodies to CbpA, PhtD and the C-terminal fragment of PhtD (PhtD C) were measured in serum samples collected at 12 (N=286) and 18 months (N=259) to evaluate the risk of subsequent pneumococcal acute otitis media (AOM) in relation to antibody concentrations.

Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics.

Background: In contrast to the other vaccine serotypes, no protection could be demonstrated in the POET study against serotype 3 acute otitis media (AOM) following primary and booster vaccination with a multi-valent pneumococcal conjugate vaccine.

Methods: AOM efficacy and immunogenicity data were reviewed. Pheno- and genotypic characteristics of different serotype 3 strains including efficacy study AOM isolates were evaluated.

Pneumococcal Haemophilus influenzae protein D conjugate vaccine induces antibodies that inhibit glycerophosphodiester phosphodiesterase activity of protein D.

Haemophilus influenzae outer membrane protein D (PD) is a glycerophosphodiester phosphodiesterase (GlpQ) activity-possessing virulence factor and a promising vaccine antigen, providing 35.3% efficacy against acute otitis media caused by nontypeable H. influenzae (NTHI) when it was used as a carrier protein in a novel pneumococcal PD conjugate (Pnc-PD) vaccine.

ELISA IgG concentrations and opsonophagocytic activity following pneumococcal protein D conjugate vaccination and relationship to efficacy against acute otitis media.

We explored the relationship between efficacy against acute otitis media (AOM) and both ELISA anti-polysaccharide IgG geometric mean concentrations (GMCs) and opsonophagocytic (OPA) geometric mean titres (GMTs) following primary and booster vaccination with pneumococcal protein D (Haemophilus influenzae-derived) conjugate vaccine. It was possible to distinguish between the OPA GMTs of low and high efficacy serotypes, however no such distinction was evident for ELISA GMCs. Also, there was a trend towards lower ELISA and OPA serotype-specific responses in subjects who developed AOM compared to controls.

Validation of a routine opsonophagocytosis assay to predict invasive pneumococcal disease efficacy of conjugate vaccine in children.

Immunological evaluation of the clinical impact of vaccines designed to protect against infection by Streptococcus pneumoniae requires measurement of serotype-specific functional antibodies. We describe the development and validation of a viable pneumococcal opsonophagocytosis assay (OPA) that can be used for routine serological analysis of paediatric immune responses after immunization. OPA seropositivity (%> or =8 threshold) reflected well invasive pneumococcal disease (IPD) effectiveness.

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.