Enabling Vaccine Delivery Platforms and Adjuvants for Malaria

Enabling vaccine delivery platforms and adjuvants with promising attributes for malaria vaccine development are reviewed within the framework of accessibility, efficacy, clinical status, cost, and cold-chain considerations. An emphasis is placed on commercially available platforms and adjuvants including virus-like particle, nanoparticle, microneedle, and mRNA vaccine delivery platforms as well as lipid vesicle, microparticle, and emulsion-based adjuvants. Strategies for addressing complications of vaccine delivery in endemic regions due to concatenate vaccination and infection, and parasite immune avoidance mechanisms are presented. Additionally, recent findings regarding how malaria infection triggers inflammatory pathways and T cell exhaustion along with negative impacts to the development of effective memory responses are described in a context relevant to vaccine development

Semicontinuous Bioreactor Production of Recombinant Butyrylcholinesterase in Transgenic Rice Cell Suspension Cultures.

An active and tetrameric form of recombinant butyrylcholinesterase (BChE), a large and complex human enzyme, was produced via semicontinuous operation in a transgenic rice cell suspension culture. After transformation of rice callus and screening of transformants, the cultures were scaled up from culture flask to a lab scale bioreactor. The bioreactor was operated through two phases each of growth and expression. The cells were able to produce BChE during both expression phases, with a maximum yield of 1.6 mg BChE/L of culture during the second expression phase. Cells successfully regrew during a 5-day growth phase. A combination of activity assays and Western blot analysis indicated production of an active and fully assembled tetramer of BChE

Pre-Erythrocytic Vaccine Candidates in Malaria

A vaccine providing sterile immunity against malaria has been shown to be possible with antigens from the pre-erythrocytic stages of malaria. Therefore, it is reasonable to focus vaccine development efforts on the pre-erythrocytic stages, consisting of both sporozoites and liver stage parasites, where it is expected that sterile immunity against the parasite can be elicited to block the development of blood stage infection, clinical disease, and resulting parasite transmission. Accordingly, we will review the preclinical and clinical studies of malaria pre-erythrocytic efforts as well as highlight the advances, trends, and roadblocks encountered in these efforts

The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’

We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials