Vaccines & Immune Biology

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.

Charani Ranasinghe of The Australian National University will test a new vaccine technology that modulates a host cytokine response to HIV vaccines. If successful, this "cytokine trap" technology may also enhance T-cell mediated immunity to other vaccine antigens, such as Tuberculosis.

Elizabeth Ryan of Colorado State University in the U.S. will screen a diverse, global set of rice varieties to identify bioactive components in the bran that augment mucosal immunity against enteric bacterial pathogens. In this project's Phase I research, Ryan and her team identified multiple mechanisms of mucosal immune induction and demonstrated that increased dietary rice bran intake reduces host susceptibility to enteric infections via enhanced gut mucosal immunity.

Harry Greenberg of Stanford University School of Medicine and the VA Palo Alto Health Care System in the U.S. will develop a new assay that evaluates the function and phenotype of plasmablasts in peripheral blood after infection or vaccination. By determining how many of these cells have mucosal-homing receptors, Greenberg believes this new test could provide an accurate measurement of mucosal immune response.

Vincenzo Casolaro of the University of Maryland School of Medicine in the United States will test the ability of a novel synthetic peptide, AT1002, to induce the pathways within the mucosa to increase the delivery of antigens. If successful, this peptide could be used as an adjuvant to increase vaccine effectiveness and lower the costs of delivering vaccines.

Ann Kurth of New York University in the U.S. will test the hypothesis that eliminating intra-vaginal practices such as douching will allow the return of healthy vaginal flora conditions which includes ideal pH and an intact vaginal mucosa. By restoring and maintaining this healthy environment, Kurth proposes that incidences of pelvic inflammatory disease and HIV infection can be reduced.

Julio Scharfstein of Universidade Federal do Rio de Janeiro in Brazil will study whether a pre-dose of captopril, an established angiotensin-converting enzyme (ACE) inhibitor and anti-hypertension drug, can increase the potency of vaccines by increasing the activation of dendritic cells.

Gustavo Fioravanti Vieira of Universidade Federal do Rio Grande do Sul in Brazil will create 3-D computer models of viral epitopes anchored to major histocompatibility complex (MHC) molecules associated with different MHC alleles to search for "generalist" epitopes. Such epitopes can be used to develop viral vaccines that are effective against a broad spectrum of pathogens.

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.

Mosquito transmitted pathogens such as dengue and malaria are a significant disease burden on the world's population. Paul Young of the University of Queensland in Australia aims to develop a novel vaccine approach that is based on blocking mosquito transmission of these disease agents rather than inducing pathogen- specific immunity.