Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting

Background: Maternal vaccines against pertussis are not yet recommended in the developing world. Besides unclear burden estimates, another concern is that transplacental transfer of maternal pertussis antibodies could result in attenuation of the immune response to whole cell pertussis (DTwP) primary vaccination series in infants. This study was taken up to determine whether higher levels of maternal pertussis antibodies attenuate immune response of infants to DTwP vaccination series given at 6-10-14 weeks of age.Methodology: A total of 261 pregnant women and their infants from four low-income settlements in Karachi, Pakistan were enrolled in this study. The study endpoints were infant antibody titers for Pertussis toxin (PTx), Filamentous hemagglutinin antigen (FHA), Pertactin (PRN) and Fimbriae type 2/3 (FIM) - from birth through 18 weeks of age. Cord blood or pre-vaccine pertussis antibody titers indicate the concentration of maternal antibodies transferred to infants. Linear regression models were used to determine the association between higher maternal antibody titers and infant immune response to DTwP vaccine. Geometric Mean Ratio (GMR) was calculated as the ratio of infant antibody titers at specified time points against the maternal antibody titers at the time of delivery.Results: At eighteen weeks of age, the adjusted β regression coefficient for PTx was 0.06 (95% CI: -0.49-0.61), FHA 0.02 (95% CI: -0.26 -0.29), PRN 0.02 (95%CI -0.38- 0.43), and FIM 0.17 (95%CI: -0.21-0.54). Among infants who received at least two doses of DTwP vaccine, higher maternal antibody titers did not have any attenuating effect on infant post-immunization antibody titers against all four pertussis antigens.Conclusion: Maternal pertussis antibodies did not attenuate infant\u27s immune response to pertussis antigens in DTwP primary vaccine given at 6-10-14 weeks of age

Chiral separations in microemulsion electrokinetic chromatography Use of micelle polymers and microemulsion polymers

Abstract In this study, microemulsions of the chiral surfactant polysodium N-undecenoyl-d-valinate (poly-d-SUV) was utilized for enantiomeric separation by investigating two approaches using polymeric chiral surfactant in microemulsion electrokinetic chromatography (MEEKC). In the first approach, poly-d-SUV was used as an emulsifier surfactant along with 1-butanol and n-heptane. Enantioseparation of anionic or partially anionic binaphthyl derivatives, anionic barbiturates, and cationic paveroline derivatives were achieved by varying the mass fraction of 1-butanol, n-heptane and poly-d-SUV. For anionic or partially anionic analytes, relatively lower mass fractions of n-heptane, and poly-d-SUV were found to give optimum chiral separations as compared to that for cationic solutes. In the second approach, the chiral microemulsion polymer was prepared by polymerizing mixtures of 3.50% (w/w) of sodium N-undecenoyl-d-valinate (d-SUV) and 0.82% (w/w) of n-heptane (core phase) at varying concentration of 1-butanol. After polymerization, the n-heptane and 1-butanol were removed to yield solvent free microemulsion polymers (MPs) which were then utilized for the separation of anionic binaphthyl derivatives and anionic barbiturates. When MPs of D-SUV were utilized for chiral separation, 1.00% (w/w) 1-butanol and 3.50% (w/w) 1-butanol was optimum for enantioseparation of (±)-BNP and (±)-BOH, respectively. On the other hand, for anionic (±)-barbiturates very low concentration of butanol (0.25%, w/w) provided optimum resolution. Compared with micellar electrokinetic chromatography (MEKC), the use of micelle polymers or microemulsion polymers in MEEKC showed dramatic enhancement for resolution of (±)-BNP, while this enhancement was less dramatic for other binaphthyls [(±)-BOH, (±)-BNA] as well as for (±)-barbiturates and (±)-paveroline derivatives. However, higher separation efficiency of the enantiomers was always observed with MEEKC than in MEKC

Nitration of H2B histone elicits an immune response in experimental animals

Histone H2B is an autoantigen that appears in circulation due to altered apoptosis/or insufficient clearance and is likely to be involved in the induction and progression of autoimmune diseases since modified-H2B is immunogenic. Our studies demonstrate that tyrosines of H2B histone spontaneously converts to free and nitrotyrosine bound protein in vivo. Commercially available H2B histone was modified with peroxynitrite in vitro. Modified H2B was found to be more immunogenic than native form in experimental animals. Furthermore, the sera of rabbits were analyzed for the native and modified forms of the H2B histone. The binding specificity of autoantibodies was characterized by competitive enzyme-linked immunosorbent assay (ELISA) and band shift assay. The free 3-nitrotyrosine in systemic lupus erythematosus sera was quantified by high-performance liquid chromatography. Peroxynitrite-modified H2B induced high titre antibodies as compared to native form which were directly proportional to the nitrotyrosine content. Furthermore, the induced antibodies showed specificity towards the immunogen and cross-reacted with tyrosine-nitrated proteins. ELISA showed preferential binding of induced anti-peroxynitrite modified H2B antibodies to modified H2B as compared to native H2B. The present study shows that peroxynitrite modification of self-antigen(s) generates neoepitopes capable of inducing modified-H2B autoantibodies in experimental animals