Nirbhay Kumar of Johns Hopkins University in the U.S. will use a technique called codon harmonization to fully and correctly express a complex malaria gamete surface protein. The sexual stages of malaria parasites have been shown to be particularly vulnerable to antibody targeting. This approach may be able to block the transmission of malaria in insect vectors.

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.

Jennifer Maynard and Nicholas Peppas of the University of Texas at Austin in the U.S. seeks to engineer proteins to be delivered by oral polymeric vaccine that specifically bind to receptors of M cells on the gut mucosa. By targeting these M cells, antigens can be introduced directly to the mucosal system, inducing a targeted, stronger immune response.

Madhu Malo of Massachusetts General Hospital/Harvard Medical School in the U.S. will investigate whether maintaining the normal intestinal commensal bacteria using oral supplementation of intestinal alkaline phosphatase (IAP), a small intestinal brush-border enzyme, will prevent or cure infection by pathogenic bacteria. A successful project would generate a universal prophylactic and therapeutic strategy against diarrheal diseases.

Sungano Mharakurwa of the Malaria Institute in Zambia proposes to take advantage of the “off-season” in regions affected by malaria. The team will identify asymptomatic carriers of the malaria parasite using a simple, non-invasive diagnostic tool using saliva samples which can be easily used by village community workers. Those individuals will be treated to eliminate the parasite before it can be transmitted during the rainy season, when malaria cases increase.

Simon Foote of the Menzies Research Institute at the University of Tasmania in Australia will use "forward genetic screening" approaches identify mutations that confer resistance after exposure to malaria parasites. The team will use this powerful information to develop drug therapies that target the human host and mimic these protective genetic effects.

Michel Gilbert of the National Research Council Canada will use the single-celled microorganism T. acidophilum to produce HIV proteins with unique sugar residues found only in archaebacteria such as T. acidophilum. By modifying these glycan structures to ones not recognized by humans, Gilbert hopes to elicit a stronger immune response against the virus.

Edward Dolk of Utrecht University in the Netherlands proposes using two-sided antibodies, which bind to HIV and to transport receptors in the epithelium. Binding these receptors will cause excretion of the HIV particles outside of the body, thereby reducing viral load.

Bryan Greenhouse of the University of California, San Francisco, will design a series of microsatellites, short DNA repeats which have variable lengths in different parasites, to track individual parasites in two regions close to malaria elimination. If successful, this approach will provide insight into parasite transmission networks and help to guide future malaria eradication efforts.

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. They also demonstrated in an animal model that oral immunization with these bacteria in a killed formulation elicited immune responses similar to those obtained by vaccination with currently licensed oral killed whole-cell cholera vaccines. In Phase II, he will further improve these strains by inducing them to express an accompanying adjuvant and conduct immunogenicity analyses and other work to prepare for a Phase I trial.

Richard Sayre of Donald Danforth Plant Science Center in the U.S. will develop and test a transgenic algae that delivers interference RNA (RNAi) elements to mosquito larvae when they feed on it. These RNAi will silence essential genes used by the larvae to develop, thus killing mosquitoes before they can transmit malaria.

Gadi Borkow of Cupron, Inc. in the U.S. will study the efficacy of using newly developed copper-oxide based filters that deactivate a wide range of viruses, including HIV-1, as a shield to enable HIV-infected mothers to breastfeed their infants without risking transmission of the virus.

Patrick Kiser of the University of Utah in the U.S. will design a vaginal gel that blocks HIV by becoming impermeable in response to the pH change induced by the presence of semen, and includes a polymer engineered to bind to HIV surface proteins to halt viral transport to susceptible tissues and HIV target cells. In this project's Phase I research, Kiser and his team engineered a synthetic polymer that has many of the properties of mucus, and demonstrated that the polymers slow or stops the movement of cells in the presence of semen. In Phase II, Kiser will focus on developing a pericoital contraceptive gel that will prevent the movement of spermatozoa into the uterus.

Kuan-Teh Jeang of the National Institutes of Health in the U.S. will investigate whether cells infected by one virus become resistant to infection from other viruses, and if this viral interference can confer protection against HIV. The team will develop an attenuated virus to test whether over-expression of viral envelope proteins within cells can confer resistance to further HIV infection.

Enterotoxigenic E. coli (ETEC) is the leading cause of diarrhea in the developing world. Roy Robins-Browne, of the University of Melbourne, in Australia will evaluate the effectiveness of a prototype vaccine that combines enterotoxin of E. coli (which lacks immunogenicity by itself) with another epitope to attract helper T cells and a lipid adjuvant to ensure delivery of the antigen directly into the cell.

Ines Atmosukarto of Lipotek Pty Ltd. in Australia proposes to develop a novel TB vaccine utilizing synthetic “nano-sacs” called liposomes that carry TB antigens and are anchored with a self-adjuvanting protein that binds to and stimulates dendritic cells.

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. In Phase I, a proof-of-concept study was performed to establish MicroCubes as a promising vaccine platform, focusing on production versatility, potential vaccine delivery routes, and efficacy for inducing an immune response in mice. In Phase II, they will investigate the broader potential of MicroCubes as a generic vaccine platform that can be used to deliver a wide range of antigens, and will use it to develop a candidate vaccine against HIV.

Golam Rabbani of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) will study the effects that a new model of indoor cooking stove with concealed combustion chambers and ventilation chimney has in reducing indoor air pollution and subsequently, reducing acute lower respiratory infections and TB in children.

Julio Scharfstein of Universidade Federal do Rio de Janeiro in Brazil will study whether a pre-dose of captopril, an established angiotensin-converting enzyme (ACE) inhibitor and anti-hypertension drug, can increase the potency of vaccines by increasing the activation of dendritic cells.

Chen Yangchao of the Chinese University of Hong Kong proposes developing a lentiviral vector that targets the entry and replication of influenza viruses in domestic chickens. The team plans to test the ability of these modified chickens to be resistant to various influenza viruses in an effort to reduce the frequency of flu epidemics in poultry and, ultimately, in humans.

Uri Selome McKakpo of the University of Ghana will develop and test a rapid dipstick test that utilizes monoclonal antibodies to detect parasite antigens present in urine of infected individuals. Using this technology, the team hopes to create a new diagnostic test for malaria that requires minimal training to use and does not depend on invasive blood samples.

Because tuberculosis manipulates host cells to resist the immune response and current drug therapies, Nigel Savage of Leiden University Medical Center in the Netherlands will utilize RNAi analysis to identify the essential pathways used by the bacteria to modify its host cell. By discovering these pathways, novel therapies can be developed to counteract this host manipulation without directly targeting the pathogen and causing the development of resistance.

To optimize the effectiveness of current anti-tuberculosis drugs, Boitumelo Semete of the CSIR in South Africa will work with collaborators to develop “sticky nanoparticles” that specifically attach to TB-infected cells. Once taken in by these cells, the nanoparticles will slowly degrade, releasing the anti-TB drugs and killing the bacteria. With this novel drug delivery system, the team aims to improve the bioavailability of the current therapies, with the possibility of shortening the treatment period for TB as well as reduce drug side effects.

Maria Lerm of Linkoping University in Sweden will test her hypothesis that TB latency is a dynamic process in which a portion of the bacilli, when ingested by macrophages, trigger a genetic program where bacteria cycle between active and latent phases. Understanding whether this dynamic cycle exists could give new insights into maintaining or targeting the latent bacteria, which is the major reservoir of TB globally.