Vaccines & Immune Biology

Craig Morita of the University of Iowa in the U.S. will engineer Salmonella and Shigella vaccine vectors to overproduce an essential antigen to stimulate gamma delta T cells, to boost mucosal immune response against these enteric pathogens.

Ifor Williams of Emory University School of Medicine in the U.S. will test the theory that a newly characterized cytokine that triggers the development of M cells can be used as an adjuvant to boost immunity in mucosal surfaces and lead to greater uptake of vaccines.

Jeremy Webb and collaborators at the School of Biological Sciences in the United Kingdom will search for unique proteins that allow pneumococcal bacteria to form biofilms on mucosal surfaces. The team will use laser capture micro-dissection "laser tweezers" to dissect these bacterial communities with the goal of finding antigens common to all serotypes and could be used as the basis for future vaccines.

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.

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.

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.

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.

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.

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.

Alec Sutherland of Arizona State University in the United States will develop and test a vaccine delivery system that uses Norovirus virus-like particles (VLPs) to deliver desired antigens directly to the gut mucosa. The self-replicating RNA in the VLP will not only encode those antigens, it will also act as an adjuvant by activating several signaling pathways for an enhanced and sustained immune response.