Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system

Previous work had shown that the immunogenicity of conjugate vaccine against group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin (LT), and with delivery systems such as chitosan derivatives. We show, in mice, that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery system allows the reduction of each of the components for the induction of antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl at titers similar to or higher than those induced by parenteral immunization. These data could affect the design of efficacious mucosal vaccines and their safety.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.