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.

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.

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.

Michael Lebens of the University of Gothenburg Institute for Vaccine Research in Sweden proposes to develop a new oral cholera vaccine using a single cholera strain that expresses antigens for both the Inaba and Ogawa serotypes and produces cholera toxin subunits that act as an adjuvant to stimulate mucosal immune activity. In this project's Phase I research, Lebens and his team successfully generated potential vaccine candidate strains that express both Ogawa and Inaba type antigens simultaneously.

Ofer Levy at Children’s Hospital Boston in the U.S. will determine whether synthetic molecules called imidazoquinolines activate newborns’ white blood cells, and could be used as candidate vaccine adjuvants to dramatically enhance immunization at birth. In this project’s Phase I research, Levy demonstrated that Toll-like Receptor-7 and -8 agonists are superior to agonists of other Toll-like receptors and to alum, an already approved vaccine adjuvant, in activating newborn immune responses in studies in vitro.

Laurel Lagenaur and the team at Osel, Inc. in the U.S. will engineer a native human vaginal Lactobacillus to secrete a potent and broadly antiviral domain antibody fragment and evaluate the microbe’s ability to prevent HIV infection in the vaginal mucosa. In this project's Phase I research, Lagenaur's team examined levels of expression of HIV-neutralizing proteins by Lactobacillus. Recently several broadly neutralizing domain antibodies have been identified.

Because human carriage of pneumococcus usually results in improved immunity to future infections without any development of disease, Stephen Gordon of the Liverpool School of Tropical Medicine in the United Kingdom will use an intranasal inoculation with a safe strain of the bacteria to study the mechanisms of mucosal immunity in the lungs and to explore the potential for a vaccine based on his findings.