Vaccines & Immune Biology

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.

Sangeeta Joshi of the Middaugh laboratory at the University of Kansas in the U.S. will develop a novel polymer vaccine composed of assembled versions of "needle" and "tip" surface proteins used by Shigella and Salmonella pathogens to trigger bacterial invasion in human intestinal cells, and test it for its ability to induce antibody 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.

Chang Yi Wang of United Biomedical, Inc. in the United States will develop and test synthetic peptide immunogens that mimic conserved sites used by HIV to gain entry to host T-cells. Mimicking the correct three-dimensional structure of these important proteins should generate antibody responses that block this initial step of HIV infection and neutralize the virus.

Tycho Speaker of Transderm Inc. in the United States, along with Juvaris Biotherapeutics, will test the efficacy of a dry microneedle skin patch loaded with malaria antigens and a novel adjuvant for its ability to stimulate a robust immune response. If successful, this painless, low-cost, no-refrigeration vaccine delivery system could increase vaccine access to at-risk populations.

Vijay Pancholi of The Ohio State University Research Foundation in the U.S. will attempt to attenuate the S. pneumonia bacteria by altering export of the GAPDH enzyme, a function thought to be essential to the bacteria's survival. Preventing export of this key enzyme will decrease bacterial virulence, allowing the attenuated strain to be used for development an affordable live vaccine for pneumococcal pneumonia.

Paul Kim of Johns Hopkins University in the U.S. will modify HIV by removing the viral genome and replacing the outer domain of the gp120 protein, used by the virus to invade host immune cells, with receptors normally used by gp120 to bind to host cells. When this modified ghost virus encounters native HIV during an infection, hidden epitopes are exposed to the host immune system, stimulating antibodies to clear the infection.

Nick Grassly of Imperial College London and colleagues at CMC-Vellore in India will try to improve the immune response to oral poliovirus vaccine among children in India by treating enteric infections before vaccination. If successful, this simple intervention could reduce the number of vaccine doses required to protect children in lower-income countries.

James Flanegan of the University of Florida in the U.S. proposes to develop a non-infectious poliovirus vaccine using encapsidated replicons or mature empty capsids that retain full immunogenicity. Either approach can be potentially used to develop a new vaccine that can be safely used in a pre- or post-eradication world.

Hajime Mori of Kyoto Institute of Technology in Japan will develop protein chips that encapsulate poliovirus-like particles (PLP) for use as a safe and effective polio vaccine. When the PLP-protein chips are orally administered, they pass through the stomach without degradation and then are gradually released into the gut to induce a strong immunity against poliovirus infection.