54 research outputs found
Immunogenicity of Self-Associated Aggregates and Chemically Cross-Linked Conjugates of the 42 kDa Plasmodium falciparum Merozoite Surface Protein-1
Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP142) was evaluated as a self-associated, non-covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP142 conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP142 self-associated aggregates, cross-linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP142 specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis
The effectiveness of financial incentives for smoking cessation during pregnancy: is it from being paid or from the extra aid?
<p>Abstract</p> <p>Background</p> <p>Financial incentives appear to be effective in promoting smoking cessation in pregnancy. The mechanisms by which they might operate however, are poorly understood. The present study examines how financial incentives for smoking cessation during pregnancy may work, by exploring pregnant women's experiences of trying to stop smoking, within and outside of a financial incentives scheme.</p> <p>Methods</p> <p>Thirty-six (n = 36) UK-based pregnant smokers (n = 36), offered standard NHS Stop-Smoking Services, of whom twenty (n = 20) were enrolled in a financial incentives scheme for smoking cessation (n = 20) and sixteen (n = 16) were not, were interviewed about (i) their motivation to stop smoking, and (ii) the factors they perceived as influencing their quitting efforts. Framework Analysis was used to analyse the data.</p> <p>Results</p> <p>Women in the two groups reported similar reasons for wanting to stop smoking during pregnancy. However, they described dissimilar experiences of the Stop-Smoking Services, which they perceived to have differentially influenced their quit attempts. Women who were incentivised reported using the services more than women who were not incentivised. In addition, they described the motivating experience of being monitored and receiving feedback on their progress. Non-incentivised women reported problems receiving the appropriate Nicotine Replacement Therapy, which they described as having a detrimental effect on their quitting efforts.</p> <p>Conclusion</p> <p>Women participating in a financial incentives scheme to stop smoking reported greater engagement with the Stop-Smoking Services, from which they described receiving more help in quitting than women who were not part of the scheme. These results highlight the complexity of financial incentives schemes and the intricacies surrounding the ways in which they operate to affect smoking cessation. These might involve influencing individuals' motivation and self-regulation, changing engagement with and provision of support services, or a combination of these.</p
Intraspecies Variation in the Emergence of Hyperinfectious Bacterial Strains in Nature
Salmonella is a principal health concern because of its endemic prevalence in food and water supplies, the rise in incidence of multi-drug resistant strains, and the emergence of new strains associated with increased disease severity. Insights into pathogen emergence have come from animal-passage studies wherein virulence is often increased during infection. However, these studies did not address the prospect that a select subset of strains undergo a pronounced increase in virulence during the infective process- a prospect that has significant implications for human and animal health. Our findings indicate that the capacity to become hypervirulent (100-fold decreased LD50) was much more evident in certain S. enterica strains than others. Hyperinfectious salmonellae were among the most virulent of this species; restricted to certain serotypes; and more capable of killing vaccinated animals. Such strains exhibited rapid (and rapidly reversible) switching to a less-virulent state accompanied by more competitive growth ex vivo that may contribute to maintenance in nature. The hypervirulent phenotype was associated with increased microbial pathogenicity (colonization; cytotoxin production; cytocidal activity), coupled with an altered innate immune cytokine response within infected cells (IFN-β; IL-1β; IL-6; IL-10). Gene expression analysis revealed that hyperinfectious strains display altered transcription of genes within the PhoP/PhoQ, PhoR/PhoB and ArgR regulons, conferring changes in the expression of classical virulence functions (e.g., SPI-1; SPI-2 effectors) and those involved in cellular physiology/metabolism (nutrient/acid stress). As hyperinfectious strains pose a potential risk to human and animal health, efforts toward mitigation of these potential food-borne contaminants may avert negative public health impacts and industry-associated losses
Assessment of Pfs25 expressed from multiple soluble expression platforms for use as transmission-blocking vaccine candidates
Relative Atomic Variation (RAV) of Elements in Lake Sediments: Lake Winnipeg and Other Canadian Lakes
Enhanced antibody responses to Plasmodium falciparum Pfs28 induced in mice by conjugation to ExoProtein A of Pseudomonas aeruginosa with an improved procedure
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