Vaccines & Immune Biology

More than a million people die of malaria each year -- most of them infants, young children, and pregnant women, and most of them in Africa. Although severe malaria has a high mortality rate, some children in areas where the disease is endemic might experience only one or two episodes of severe illness before they become resistant to further bouts of the disease. Dr.

Dr. Shaw is leading a consortium of investigators from clinical and laboratory research sites in Africa, the Caribbean, and the United States. They are conducting a comprehensive, integrated analysis of humoral and cellular responses to HIV-1 in people in early and acute stages of infection. Investigators are basing their work on the hypothesis that HIV-1 leads to chronic, persistent infection rather than a rapidly lethal disease because elements of the human immune system partially constrain viral replication over long periods.

Due to differences in their immune systems, individuals respond to malaria in different ways. While some die, others survive, and still others are infected without becoming ill. Understanding how and why some people naturally resist malaria may help lead to the development of an effective vaccine against the disease. Dr. Kwiatkowski is leading the Malaria Genomic Epidemiology Network, or MalariaGEN, an international partnership of malaria research groups.

Acute respiratory infections, often due to Streptococcus pneumoniae (pneumococcus), are a primary cause of death in young children in developing countries. A new vaccine effectively prevents the most serious form of pneumococcal disease and also reduces nasopharyngeal colonization with pneumococci. Because only some people who are infected become ill, researchers must study tens of thousands of vaccinated individuals over a long period of time to determine whether the vaccine guards against disease. Dr.

A subset of women who apparently are resistant to HIV infection may provide scientists with the genetic and immune system information they need to advance vaccine and drug development. Since 1985, investigators have tracked groups of commercial sex workers in Kenya who do not become infected with HIV despite repeatedly having sex without condoms. If investigators can understand what constitutes and results in protective immunity against HIV, they may be able to replicate it through vaccines. Dr.

Tuberculosis (TB) is a major health problem, especially in developing countries. Dr. Kaufmann is leading an international consortium that is studying differences in immune system responses between people exposed to TB who never become sick and those who develop the disease, focusing particular attention on people infected with both HIV and TB in endemic African countries.

Attenuated vaccines, composed of weakened organisms incapable of causing disease, provide prolonged exposure to antigens and have proven effective against several viral or bacterial diseases. Dr. Kappe's team is attempting to extend this concept to a malaria vaccine. In the case of malaria, disease develops when the malaria sporozoite – the form of the parasite that is transmitted from mosquitoes to humans – enters the bloodstream and moves to the liver. There, it grows and divides into thousands of parasites that invade and destroy red blood cells, causing disease. Dr.

Dr. Shattock and collaborators in the U.K. and South Africa will attempt to develop an HIV vaccine that stimulates immunity to the virus in the lining of the vagina. The investigators hypothesize that an HIV vaccine will be most effective at the site where the virus enters the body. Innovative combinations of vaccine antigen formulas and delivery technologies will be used to develop a potentially potent and effective vaccine. The vaccine will be designed to be delivered via low-cost vaginal gels or via silicone rings that fit inside the vagina and can be self-administered.

Dr. Steinman's team is developing vaccines that stimulate the immune system's dendritic cells, which are known to play an important role in stimulating protection against infectious diseases. One approach is to engineer vaccine antigens into monoclonal antibodies against receptors on the surface of dendritic cells. A secondary approach involves engineering genes for the antigens of interest into the yellow fever virus. The project will focus on creating experimental vaccines for a range of diseases, including HIV and malaria.

Dr. Hill and his colleagues are exploring a novel approach to enhancing the ability of plasmid DNA, pox, or adenoviral vectored vaccines to stimulate strong immune responses. Building on recent advances in understanding of pattern recognition molecules as well as intracellular signaling pathways, investigators are working to add intracellular adjuvants (molecular signals that have the potential to enhance immunogenicity) to the vaccine vectors. Also being explored is the effect of adding molecules designed to inhibit regulatory pathways that may be limiting protective immune response.