Vaccines & Immune Biology

Dennis Hartigan-O'Connor of the University of California at San Francisco in the U.S. will test whether expanding Th17 cell populations, a subset of CD4 T cells that protect the gastrointestinal tract against microbes, can augment the gut's general defenses and protect against the acute and chronic effects of HIV.

Louis Schofield of The Walter and Eliza Hall Institute in Australia will develop a synthetic saccharide-conjugated vaccine that would provide immunity against GPI, a toxin produced by the malaria parasite that is a major determinant in the severity and fatality of the disease. This project’s Phase I research demonstrated preclinical safety and efficacy of a synthetic anti-toxin vaccine for malaria, showing that the oligosaccharide target was conserved across all malaria species and life stages.

Because a robust immune response can actually foster HIV replication and spread, Joseph (Mike) McCune at the University of California at San Francisco in the U.S. proposed that building tolerance to HIV will hinder disease progression better than vaccinations that activate the immune system and trigger HIV activity. This project’s Phase I research demonstrated in a non-human primate model that tolerance to SIV could be induced by introducing SIV antigens to fetuses in utero.

Brendan Wren of the London School of Hygiene & Tropical Medicine in the UK will test a new bacterial synthesis method, Protein Glycan Coupling Technology. This method uses bacteria to attach proteins to glycans to produce glycoconjugate vaccines, and it could lead to an improved vaccine against pneumococcal disease. This project’s Phase I research demonstrated that a Streptococcus pneumoniae capsular polysaccharide could be transferred to a carrier protein in E. coli.

Mark Davis of Stanford University in the U.S. will develop a new method to assess specific T cell responses to vaccinations. Using combinations of labeled tetramers to identify many types of T cell responses, Davis hopes to create better and more comprehensive assessments of immunity generated by vaccines. This project's Phase I led to the development of a new way to color-code T cells as a way to visually quantify immune response to an influenza vaccine.

Dirk Linke of the Max Planck Society in Germany seeks to identify and classify all the molecules that make up the cell wall of gram-negative bacteria, which causes a major portion of infectious diseases. By recognizing common elements among these molecules, a broad-range vaccine could be developed to protect against a number of these diseases.

To stop the spread of tuberculosis, scientists are working to develop methods that prevent new infections and also eliminate infection in the huge reservoir of people who already are infected with MTB. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent MTB from causing disease have the potential to significantly reduce illness, death, and disease transmission. Dr.

Each year, about a half-million women, 80 percent of them living in low-income countries, develop cancer of the cervix. The disease kills 250,000 women annually, and is the second leading cause of cancer deaths among women living in less developed countries. Nearly all cases of cervical cancer are caused by infection with human papillomavirus (HPV), the most common viral infection of the reproductive tract. Dr.

People infected with many serious illnesses, including tuberculosis and hepatitis C, may show no symptoms of disease for long periods of time. These inactive, or "latent," infections, however, can develop into active disease without warning, and also can be passed on to others. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent them from causing disease have the potential to significantly reduce illness, death, and disease transmission. Dr.

Dr. Baltimore’s team is exploring a new way of stimulating the immune system to fight infectious diseases, focusing on HIV. The premise of this project is that for some infections, including HIV, the immune system’s natural responses are inherently inadequate, and the traditional approach of using vaccines to stimulate and boost these responses is likely to be ineffective. As an alternative, Dr. Baltimore and his colleagues propose to "engineer immunity," that is, use genetic engineering methods to produce immune cells that will make specific antibodies to fight off infection.