Infectious Disease

Paul Kelly of Queen Mary, University of London in the United Kingdom and the University of Zambia will test the idea that retinoic acid (a form of vitamin A) given with an oral vaccine will boost the mucosal immune response. If successful, vitamin A derivatives could be used as adjuvants for oral vaccines that target childhood diarrhea. In this project's Phase I research, Kelly was able to demonstrate that retinoic acid enhances gut IgA responses to an oral typhoid vaccine in Zambian adults.

Roozbeh Ghaffari, Patrick Beattie, Jason Rolland and Jeff Carbeck of Diagnostics For All & MC10 Inc. will develop disposable paper-based diagnostics devices embedded with optoelectronics, allowing quantitative colorimetric analysis for HIV viral load monitoring. This platform addresses practical limitations of current image capture methodologies and eliminates the need for external readers.

Yingjie Lu and Richard Malley of Children's Hospital Boston in the U.S. will develop a bivalent pneumococcal and typhoid vaccine by using a new technology to include three highly conserved pneumococcal antigens and the well-established Vi polysaccharide antigen that provides protection against typhoid fever. The team will test the ability of this vaccine to induce strong humoral and cellular immune responses against both pneumococcus and the causative agent of typhoid fever, Salmonella Typhi.

Federica Marelli-Berg of Imperial College London in the United Kingdom will test the theory that using "homing factors" as vaccine adjuvants will induce the development of memory T cells, thereby generating site-specific immunity against pathogens in the gut. This project's Phase I research demonstrated that helminth infection in the presence of a homing factor led to an enhanced immunological effect. In Phase II, Marelli-Berg, now at the Queen Mary University of London, aims to develop this observation into a vaccination protocol for clinical application in this and other infections.

Fasséli Coulibaly of Monash University in Australia will design a vaccine platform based on protein crystals (MicroCubes) produced by insect viruses to produce new and more potent vaccines with increased stability, obviating the need for refrigerated storage. The crystal structure will be engineered to present multiple antigens that will then be tested for their ability to induce an effective immune response.

Ranjan Nanda and Virander Chauhan of the International Centre for Genetic Engineering & Biotechnology in India will gather breath samples from tuberculosis patients and use gas chromatography-mass spectrometry (GC-MS) to identify and track unique molecules such as volatile organic compounds (VOCs) that might serve as biomarkers to diagnose tuberculosis. The overall goal is to then create a handheld "electronic nose" to diagnose the disease in resource-poor settings.

William Royea of Next Dimensions Technology, Inc., in the U.S. seeks to develop a point-of-care breath analyzer. The proposed system aims to use an array of chemical films that are sensitive to changes in electrical conduction as a result of volatile organic compounds (VOCs) produced by tuberculosis (TB). In this project's Phase I research, Royea and his team demonstrated proof-of-concept for detecting breath-based biomarkers of TB in a clinical setting.

William Gordon and collaborators at Tetragenetics, Inc. in the U.S. propose using T. thermophilia, a fresh-water protozoa commonly used in basic research, to produce malaria antigens in a crystalline protein gel. The close evolutionary relationship between T. thermophilia and protozoan malaria parasites may allow the antigens to retain their natural conformation. In this way, multiple vaccine components can be readily harvested as a single, low-cost, high-potency vaccine formulation. This project's Phase I research demonstrated that T.

Because HIV infection activates naturally-dormant endogenous retroviruses (ERV) in human cells, Jonah Sacha will target T cells against these ERV antigens. Such targeting to eliminate HIV infected cells could be the basis for new host-directed vaccines. In this project's Phase I research, Sacha and collaborators demonstrated that ERV-specific antibodies are specifically triggered by infection with an exogenous retrovirus like SIV or HIV.

Reto Brun (Swiss Tropical and Public Health Institute) and Isabel Roditi (University of Bern) in Switzerland seek to identify small molecules that prematurely induce African trypanosomes, which are parasites that cause fatal sleeping sickness, to differentiate into the life stages necessary for transmission of the parasite. Forcing this transformation within the mammalian host could be the basis for new methods to kill trypanosomes, and this concept might be applied to other vector-borne disease .