Awards

Juliana Cassataro of the Universidad Nacional de San Martín-CONICET in Argentina will test whether the bacterial protease inhibitor Omp19 can make vaccines more effective when they are administered orally. Oral delivery of vaccines is far simpler than by injection, which is particularly useful in low-resource settings, and it may also stimulate mucosal immunity making them more effective against some diseases. However, most vaccines administered orally are degraded in the stomach or do not induce a sufficient immune response to protect against the disease. In Phase I, while at the Universidad de Buenos Aires-CONICET, they discovered that Omp19 protects antigens from degradation and serves as an adjuvant, contributing to induction of both a mucosal and systemic immune response in mice orally immunized with proteins from the Salmonella bacterium and the Toxoplasma parasite, both of which have mucosal routes of infection. In Phase II, they will extend their mechanistic studies in order to move towards a Phase I clinical trial, and evaluate the ability of Omp19 to help induce an immune response in mice upon oral vaccination against Enterotoxigenic E. coli (ETEC), which is the most common cause of bacterial diarrhea in children from developing countries.

Giulietta Saletti of the International Vaccine Institute in the Republic of Korea will work to develop an assay test that binds to tissue-specific cell markers to not only measure the concentration of anti-body secreting cells, but also identify which of those cells are targeted to mucosal tissues. If successful, this simple test that requires a small blood sample can be used in low-resource settings to measure mucosal immune responses to vaccines in infants and children.

Sylvia van den Hurk and Sidney Hayes of the University of Saskatchewan in Canada proposes that bacteriophage lambda, a virus that invades bacterial cells and uses the host's genome to replicate, can be used as a vector to deliver DNA vaccines into targeted cells. Van den Hurk will test this lambda delivery platform its ability to induce long-term systemic and mucosal immune responses.

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.

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.

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. Phase II studies will test the effects of dietary rice bran and rice varietal differences in bacterial and viral pathogen disease prevention models. These studies will begin the process of identifying quantitative traits that modify mucosal immunity and that can be included in rice crop improvement programs.

Carlos Alberto Guzman of the Helmholtz Centre for Infection Research in Germany with Claus-Michael Lehr and Steffi Hansen of the Helmholtz-Institute for Pharmaceutical Research will develop and test a vaccine platform that uses a nanoparticle that mimics pollen, which has been shown to be able to penetrate the skin through hair follicles. The nanoparticle will burst upon contact with human sweat, releasing adjuvants and antigens to deliver a vaccine by targeting dendritic cells that surround hair follicles.

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.

Youngnim Choi of Seoul National University in the Republic of Korea will test whether Fusobacterium nucleatum, a common bacteria often found in human mouths, can be used to deliver antigens to the oral mucosa. This bacteria has the ability to invade epithelial tissues, and Choi hopes to engineer a strain to express a vaccine antigen when given under the tongue to induce both antibody production and a strong cell-mediated immune response.

Douglas Watson and colleagues of SRI International will engineer probiotic bacteria that produce Vitamin A to test the hypothesis that these bacteria will stimulate healthy immunity in the GI tract and reduce the impact of diarrheal diseases.