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1.
Hum Vaccin Immunother ; 12(2): 393-402, 2016.
Article in English | MEDLINE | ID: mdl-26618243

ABSTRACT

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.


Subject(s)
Antibodies, Bacterial/blood , Hydrolases/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/adverse effects , Pneumococcal Vaccines/immunology , Streptolysins/immunology , Antibodies, Bacterial/immunology , Bacterial Proteins/immunology , Child, Preschool , Female , Gambia , Humans , Male , Pneumococcal Infections/immunology , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/immunology , Vaccination , Vaccines, Conjugate/immunology
2.
Genes Immun ; 8(6): 456-67, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17611589

ABSTRACT

We investigated the role of DC-SIGN (CD209), long pentraxin 3 (PTX3) and vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in susceptibility to pulmonary tuberculosis (TB) in 321 TB cases and 347 healthy controls from Guinea-Bissau. Five additional, functionally relevant SNPs within toll-like receptors (TLRs) 2, 4 and 9 were typed but found, when polymorphic, not to affect host vulnerability to pulmonary TB. We did not replicate an association between SNPs in the DC-SIGN promoter and TB. However, we found that two polymorphisms, one in DC-SIGN and one in VDR, were associated in a nonadditive model with disease risk when analyzed in combination with ethnicity (P=0.03 for DC-SIGN and P=0.003 for VDR). In addition, PTX3 haplotype frequencies significantly differed in cases compared to controls and a protective effect was found in association with a specific haplotype (OR 0.78, 95% CI 0.63-0.98). Our findings support previous data showing that VDR SNPs modulate the risk for TB in West Africans and suggest that variation within DC-SIGN and PTX3 also affect the disease outcome.


Subject(s)
C-Reactive Protein/genetics , Cell Adhesion Molecules/genetics , Lectins, C-Type/genetics , Polymorphism, Single Nucleotide , Receptors, Calcitriol/genetics , Receptors, Cell Surface/genetics , Serum Amyloid P-Component/genetics , Adolescent , Adult , C-Reactive Protein/metabolism , Case-Control Studies , Cell Adhesion Molecules/metabolism , Female , Genetic Predisposition to Disease , Genotype , Guinea-Bissau , Haplotypes , Humans , Lectins, C-Type/metabolism , Male , Mycobacterium tuberculosis , Receptors, Calcitriol/metabolism , Receptors, Cell Surface/metabolism , Serum Amyloid P-Component/metabolism , Toll-Like Receptors/genetics , Toll-Like Receptors/metabolism , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/metabolism
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