Infectious Disease

Firdausi Qadri of ICDDR,B in Bangladesh will attempt to develop an oral vaccine for tuberculosis that uses transgenic rice seeds to express recombinant antigenic proteins that will induce immunity not only in the gastrointestinal tract but also in the respiratory mucosa.

Shiladitya DasSarma will lead a team at the University of Maryland, Baltimore in the U.S. to develop an inexpensive, safe, and effective oral vaccine against invasive Salmonella disease using gas-filled bacterial vesicles. The project seeks to produce a salt-encased, shelf-stable vaccine requiring no refrigeration for distribution worldwide.

Ian Matthews of Cardiff University in the United Kingdom proposes to develop a self-sampling micro-needle patch device for the collection of small volumes of blood. Micro-needles will be fabricated using Deep Reactive Ion Etching. The device will permit non-refrigerated transport of collected blood for subsequent assays for diagnosis of infectious disease.

Anton Middelberg of the University of Queensland in Australia proposes to develop a new vaccine for rotavirus by the directed self-assembly of a safe virus-like particle in industrial reactors. The approach uses low-technology engineering methods suitable for the developing world, ensuring relevance to the communities most in need of vaccine.

Alison Hill and Daniel Scholes Rosenbloom of Harvard University in the U.S., working with Seyed Alireza Rabi and Greg Laird of Johns Hopkins University in the U.S., propose to engineer a gene therapy that delivers a viral transcription factor to reactivate CD4 cells that are latently infected with HIV along with a suicide gene that is triggered by HIV protein production to effectively kill the infected cells. This therapy could allow complete clearance of HIV from the body and a permanent cure for HIV infection.

R. Paul Johnson of Emory University in the U.S. is using single-cell transcriptional profiling to identify unique biomarkers expressed in CD4+ T cells latently infected with HIV or the simian equivalent SIV. Latent infection of long-lived cells enables the viruses to survive current drug treatments, and makes the disease very difficult to cure. In Phase I, while working at Harvard Medical School in the U.S., they developed a robust high-throughput technique to identify viral genes expressed in single cells and tested it on SIV-infected macaques.

Andres Finzi of the Centre Hospitalier de l'Université de Montréal in Canada will develop a system called "reverse fusion" in which viral-like particles that incorporate the HIV receptor CD4 and its co-receptors CCR5 and CXCR4 fuse specifically with HIV-infected cells to deliver toxic genes that kill the HIV-infected cells.

Mario Ostrowski of the University of Toronto in Canada will test the theory that alterations of host cells by HIV might also activate human endogenous retroviruses in the same cells. Ostrowski will express antigens of an endogenous retrovirus to study whether they might also mark HIV infected cells, providing a basis for the development of a new HIV vaccine.

Kathryn Miller-Jensen of Yale University in the U.S. will test the hypothesis that latently infected HIV cells produce different protein phosphorylation signatures than uninfected cells in response to drug treatments. Identifying these latent HIV cells will enable the design of new therapies that selectively target and purge these latent reservoirs.

Russell Poulter of the University of Otago in New Zealand will use a microbial biosynthesis platform to develop cyclic analogues of the viral protein Tat, which is major regulator of HIV transcription, and test their ability to activate latent HIV. The reactivated HIV would be susceptible to retroviral therapies enabling comprehensive killing of HIV infected cells.