Glycoconjugate vaccines and immune interference: A review.
ABSTRACT Bacterial polysaccharide-protein conjugate vaccines (Haemophilus influenzae type b [Hib], pneumococcal and meningococcal conjugates) have revolutionized pediatric vaccination strategies. The widely used carrier proteins are tetanus toxoid (TT), diphtheria toxoid (DT) and diphtheria toxoid variant CRM197 protein, DT conjugates being in general less immunogenic. Multivalent conjugates using TT were found to be at risk for reduced polysaccharide responses, whilst multivalent CRM197 conjugates are at lower risk for this, but may be at higher risk of inducing bystander interference, particularly affecting Hib and hepatitis B immune responses. Novel carriers avoiding these issues could enable the further development of pediatric schedules and combinations.
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ABSTRACT: An open, non-randomised study was undertaken in England during 2011-12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly (P<0.001) according to MCC vaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39-173; n=14) compared to those receiving two MCC-CRM (418; 95% CI, 325-537; n=82), two MCC-TT (277; 95% CI, 223-344; n=79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322-949; n=18). The same group also had the lowest Hib geometric mean concentrations (0.60μg/mL, 0.27-1.34) compared to 1.85μg/mL (1.23-2.78), 2.86μg/mL (2.02-4.05) and 4.26μg/mL (1.94-9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible. Copyright © 2014. Published by Elsevier Ltd.Vaccine 12/2014; 33(5). DOI:10.1016/j.vaccine.2014.12.018 · 3.49 Impact Factor
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ABSTRACT: Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens.Vaccine 09/2011; 29(47):8689-95. DOI:10.1016/j.vaccine.2011.08.109 · 3.49 Impact Factor
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ABSTRACT: The present paper examines the atmospheric pollution in the Jiu-Valley coal mining region of Romania. It identifies: polluting sources, pointing out the pollution favourizing conditions; the pollution impacts; and measures for short-, middle-, and long-term which could be taken in order to obtain a sustainable future development of this region. The importance of the problems presented in this paper is emphasized by the fact that beside cokeable and energetical coal reserves, this region has a high touristic potential the whole yearEnergy Conversion Engineering Conference, 1996. IECEC 96. Proceedings of the 31st Intersociety; 09/1996