Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Fraser’s Magazine and the Instability of Literary Fashion

This chapter examines the relationship between literature and fashion in one of the most influential nineteenth-century literary periodicals, Fraser’s Magazine. Established in 1830 under the editorship of William Maginn, Fraser’s became known for its scathing satirical treatment of ‘fashionable novels’ and the cult of dandyism, most notably embodied by Edward Bulwer-Lytton. Yet texts such as Thomas Carlyle’s Sartor Resartus (1833–4) and William Thackeray’s Yellowplush Papers (1837), both serialized in Fraser’s during the 1830s, express a more ambivalent fascination with the analogy between literature and fashion than their satirical mode might suggest. Fashion in clothing becomes a productive metaphor for considering the nature of literary production within an expanding market economy, characterized by the proliferation of periodicals and other forms of print ephemera