Complement C3d Conjugation to Anthrax Protective Antigen Promotes a Rapid, Sustained, and Protective Antibody Response

B. anthracis is the causative agent of anthrax. Pathogenesis is primarily mediated through the exotoxins lethal factor and edema factor, which bind protective antigen (PA) to gain entry into the host cell. The current anthrax vaccine (AVA, Biothrax™) consists of aluminum-adsorbed cell-free filtrates of unencapsulated B. anthracis, wherein PA is thought to be the principle target of neutralization. In this study, we evaluated the efficacy of the natural adjuvant, C3d, versus alum in eliciting an anti-PA humoral response and found that C3d conjugation to PA and emulsion in incomplete Freund's adjuvant (IFA) imparted superior protection from anthrax challenge relative to PA in IFA or PA adsorbed to alum. Relative to alum-PA, immunization of mice with C3d-PA/IFA augmented both the onset and sustained production of PA-specific antibodies, including neutralizing antibodies to the receptor-binding portion (domain 4) of PA. C3d-PA/IFA was efficacious when administered either i.p. or s.c., and in adolescent mice lacking a fully mature B cell compartment. Induction of PA-specific antibodies by C3d-PA/IFA correlated with increased efficiency of germinal center formation and plasma cell generation. Importantly, C3d-PA immunization effectively protected mice from intranasal challenge with B. anthracis spores, and was approximately 10-fold more effective than alum-PA immunization or PA/IFA based on dose challenge. These data suggest that incorporation of C3d as an adjuvant may overcome shortcomings of the currently licensed aluminum-based vaccine, and may confer protection in the early days following acute anthrax exposure

Concordant and discordant associations between rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis based on all hospitalizations in Sweden between 1973 and 2004

Objectives. To quantify the sibling risk of RA, SLE and AS. To analyse the concordant and discordant associations between RA, SLE and AS

Anti-flagellin antibody responses elicited in mice orally immunized with attenuated Salmonella enterica serovar Typhimurium vaccine strains

In the present study we investigated the flagellin-specific serum (IgG) and fecal (IgA) antibody responses elicited in BALB/c mice immunized with isogenic mutant derivatives of the attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) SL3261 strain expressing phase 1 (FliCi), phase 2 (FljB), or no endogenous flagellin. The data reported here indicate that mice orally immunized with recombinant S. Typhimurium strains do not mount significant systemic or secreted antibody responses to FliCi, FljB or heterologous B-cell epitopes genetically fused to FliCi. These findings are particularly relevant for those interested in the use of flagellins as molecular carriers of heterologous antigens vectored by attenuated S. Typhimurium strains

Patterns of shell repair in articulate brachiopods indicate size constitutes a refuge from predation

The cost of overcoming prey defenses relative to the value of internal tissues is a key criterion in predator/prey interactions. Optimal foraging theory predicts: (1) specific sizes of prey will result in the best returns to predators, and (2) there will often be a size at which the cost/benefit balance is low enough to effectively exclude predation. Data presented here on styles of repaired shell damage and size at which injury had been sustained was collected from samples of terebratulide brachiopods from the Antarctic Peninisula (Liothyrella uva), Falkland Islands (Magellania venosa and Terebratella dorsata) and Chile (M. venosa). The predominant form of damage on shells was indicative of predators attacking the valve margins. The modal size for repaired damage was more than 10 mm smaller than the modal size for the overall size distribution in each species and there were no repaired attacks in the largest size classes of any species. These data suggest that size forms a refuge from predation, as would be predicted by optimal foraging theory. The optimal sizes that predators appeared to attack vary between species, as do the sizes that provided a refuge from predation. High levels of multiple repairs (19% of the M. venosa population from the Falkland Islands sampled had 2 or more repairs) suggest that the mortality following attack is low, suggesting that many predators abandon their attacks

Petrogenesis of alkalic and calcalkalic volcanic rocks of Mormon Mountain Volcanic Field, Arizona

The Cenozoic Mormon Mountain Volcanic Field (MMVF) of northern Arizona is situated in the transition zone between the Basin and Range and the Colorado Plateau. It is composed of alkalic to sub-alkalic basalts and calcalkalic andesites, dacites, and rhyodacites. Despite their spatial and temporal association, the basalts and the calcalkalic suite do not seem to be co-genetic. The petrogenesis of primitive MMVF basalts can be explained as the result of different degrees of partial melting of a relatively homogenous, incompatible element-enriched peridotitic source. The variety of evolved basalt types was the result of subsequent fractional crystallization of olivine, spinel, and clinopyroxene from the range of primitive basalts. Crustal contamination seems to have occurred, but affected only the highly incompatible element abundances. The formation of MMVF calcalkalic rocks is most readily explained by small to moderate amounts of partial melting of an amphibolitic lower crust. This source is LREE-enriched but depleted in Rb and relatively unradiogenic Sr ( 87 Sr/ 86 Sr ∼0.7040). Calcalkalic rhyodacites may also be derived from andesitic parents by fractional crystallization. The overall petrogenesis of the MMVF complex is the result of intra-plate volcanism where mantle-derived magmas intrude and pass through thick continental crust.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47345/1/410_2004_Article_BF00376335.pd