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

Grandchild Care, Intergenerational Transfers, and Grandparents’ Labor Supply

Published in Review of Economics of the Household https://doi.org/10.1007/s11150-013-9221-x</p

Trends in the prevalence of grandparents living with grandchild(ren) in selected European countries and the United States

Research from the United States has shown significant increases in the prevalence of three-generation households and in households consisting solely of grandparents and grandchildren. Such shifts in household composition, which are associated with socio-economic disadvantage, may reflect the activation of grandparents as a latent network of support in response to social and demographic changes such as rising partnership disruption. However, to date, little is known in Europe about trends in grandparent households or whether these households are also likely to be disadvantaged. Moreover, we know little about how the familistic and defamilised policy environments in Europe may affect the activation of such latent kin networks. Employing the Integrated Public Use Microdata Series—International and the Office for National Statistics’ Longitudinal Study for England and Wales, we used multivariate techniques to investigate changes in prevalence over time in co-residence with a grandchild across Austria, England and Wales, France, Greece, Portugal, Romania, and the United States. We expected increases in grandparent households in Portugal and Greece, familistic societies with few public alternatives to family support. However, only Romania (like the US) showed an increase in the percentage of people aged 40 and over co-residing with their grandchildren in three-generation households between the late 1970s and 2002. Given rises in poverty and limited support for low-income families in Romania, rises in grandparent coresidence may reflect a coping strategy among poorer families to increasing financial hardship. Regardless of the trends, grandparent households in all the countries studied remained associated with socio-economic disadvantag