Infectious Disease

R. Paul Johnson of Emory University in the U.S. is using single-cell transcriptional profiling to identify unique biomarkers expressed in CD4+ T cells latently infected with HIV or the simian equivalent SIV. Latent infection of long-lived cells enables the viruses to survive current drug treatments, and makes the disease very difficult to cure. In Phase I, while working at Harvard Medical School in the U.S., they developed a robust high-throughput technique to identify viral genes expressed in single cells and tested it on SIV-infected macaques.

Yong Zhang of the National Institute for Viral Disease Control and Prevention in China will characterize vaccine-derived polioviruses (VDPV), which emerge from the widely used oral polio vaccine and can cause disease outbreaks, to aid surveillance and eradication efforts. Polio has been largely eradicated from many countries by vaccination. However, the vaccine itself is an attenuated form of the poliovirus that can revert back to a virulent form.

Hossam Haick of Technion - Israel Institute of Technology in Israel is developing a sensing plaster that can be stuck on the chest to detect volatile biomarkers emitted through the skin for self-diagnosis of tuberculosis even at early stages. The presence of tuberculosis will be signaled by colored LEDs. In Phase I, they evaluated different materials and selected non-toxic nanomaterial-based sensors. They also performed a study of healthy people and tuberculosis patients and identified several candidate volatile compounds that could be detected by the sensors.

Ian Jones of the University of Reading in the United Kingdom will investigate new methods to produce empty poliovirus capsids. These are virus-like particles that stimulate the same immunity as poliovirus itself but are completely non-infectious. A successful technology could offer cost and safety benefits leading to the replacement of traditional polio vaccines. In Phase I, he provided proof-of-concept for efficient assembly of empty viral capsids in vitro by testing different approaches to reduce the activity of the 3C enzyme, which has been associated with toxicity.

Sara Richter of the University of Padua in Italy will develop a therapeutic to completely clear HIV from the body by targeting a proviral DNA structural motif found in both actively and latently infected host cells. In Phase I they analyzed a highly conserved DNA structural motif of four guanine nucleotides (G-4) found in the integrated HIV-1 proviral DNA and found that it regulates proviral transcription and is likely involved in latent infection.

Ralph Tripp at the University of Georgia in the U.S. will identify genes that, when inhibited, enhance viral replication in the host cell lines used in the manufacture of vaccines in order to reduce the cost of vaccine production. In Phase I, he performed RNA interference screens to identify 21 host genes that, when inhibited, could enhance poliovirus replication and thereby vaccine production. In Phase II, Tripp will broaden his approach to vaccine production against rotaviruses, which cause substantial childhood mortality particularly in developing countries.

Kyu Rhee of Weill Cornell Medical College in the U.S. will test the theory that the tuberculosis (TB) bacterium uses protein-based structures termed metabolosomes to enter into, maintain, and exit from latency or non-replication. Understanding how metabolosomes work will aid in development of drugs that target TB. This project's Phase I research demonstrated that latent or non-replicating M. tuberculosis undergo a metabolic remodeling that is accompanied by the reversible formation of enzyme-based metabolosomes.

Miguel Prudencio of Instituto de Medicina Molecular in Portugal  will test the theory that modified live rodent malaria parasites (P. berghei) can be used in a vaccine to elicit a strong immune response in humans without being able to infect human red blood cells and cause illness.

Shi-hua Xiang of the Dana Farber Cancer Institute in the U.S. proposed engineering Lactobacillus, bacteria which normally reside in the human genital and gastrointestinal tract, to carry anti-HIV agents such as neutralizing antibodies, peptides, or other inhibitors. He and his colleagues hypothesized that introducing the engineered bacteria into the gastrointestinal tract would allow the bacteria to colonize and provide long-lasting protection against the virus.

Vojo Deretic of the University of New Mexico in the U.S. proposed that autophagy, a process by which cells destroy cellular components and intracellular pathogens, can be induced through drug therapy to not only destroy the HIV virus in infected cells, but also to block its transmission from dendritic cells to T cells. This project's Phase I research demonstrated that autophagy can destroy HIV, block dendritic to T cell transfer of HIV, and promote antigen presentation by dendritic cells.