Vaccines & Immune Biology

Vaccines are urgently needed to slow the spread of HIV and hepatitis C virus (HCV), which together infect an estimated 240 million people, most of them in developing countries. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Deng and his colleagues are working to improve techniques for creating mouse models with immune systems and livers that are similar enough to humans to allow testing of potential HIV and HCV vaccines.

Hepatitis C virus (HCV) is a major cause of liver diseases, including cirrhosis and liver cancer. Treatment for chronic hepatitis C is often out of financial reach for people in developing countries, and there is no vaccine against the virus. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Balling's team, partnering with Dr. Di Santo's group at the Institut Pasteur in France, is working toward the development of mice with livers and immune systems that are similar to those of humans.

To develop new vaccines against some of the world's biggest killers, including HIV, malaria, and tuberculosis, scientists must be able to evaluate promising candidates. Some of the most promising potential vaccines, are made from weakened live versions of the infectious agent. As a result, they cannot be studied in human trials unless researchers can be confident that the weakened vaccines will be safe. Dr.

Most vaccines are delivered by injection, which increases the risk that HIV, hepatitis, and other serious diseases may be transmitted by syringes and needles that are not sterile. Dr. Alonso's team is working to develop a new generation of delivery systems that can easily and effectively carry hepatitis B vaccine through the mucosal lining of the nose. In addition, the team is evaluating whether these delivery systems and the vaccine they carry can be freeze-dried into an inhaled powder that could be stored without refrigeration.

Vaccine delivery systems that target specific areas of the body have the potential to be especially effective against some types of infection. For example, inhaled vaccines may better guard against respiratory diseases, such as tuberculosis, and those that commonly infect the tissues of the nose and throat, such as diphtheria. Dr. Edwards is leading a multidisciplinary team using materials science technologies combined with infectious disease, device, and toxicology expertise to reformulate tuberculosis and diphtheria vaccines into aerosol sprays that can be inhaled.

Many serious infections, such as the measles virus, can enter the body through inhalation. Vaccine delivery systems that can target respiratory mucosal tissue and stimulate immune response there have the potential to be particularly effective against these types of infections. Collaborating with an international group that includes the Serum Institute of India (SII), the U.S. Centers for Disease Control and Prevention (CDC), the University of Colorado, and private companies, Dr.

Vaccines that can be delivered without needles have the potential to be simpler to administer and less prone to spreading infection. Dr. Baker's team is developing a new way of preparing vaccines so that they can be given as nasal drops. These nanoemulsion-based vaccines use non-toxic lipid droplets less than 200 nanometers in diameter that are absorbed through the mucosal surfaces of the nostrils. They can be easily produced using an extrusion process available worldwide and are antimicrobial, eliminating the need for preservatives or refrigeration.

In the developing world, infections in the respiratory and intestinal tracts are major causes of sickness and death, especially among children. Vaccine delivery systems that can target respiratory or intestinal mucosal tissue and stimulate immune response there have the potential to be particularly effective against these infections. Dr. Lo's project addresses two needs: the development of vaccine delivery systems that do not require needles and the design of systems that target specific tissues in the body. Using influenza vaccination as a model, Dr.

To maintain stability and viability, most childhood vaccines must be kept cool – both heat and freezing can ruin them. Drs. Sarkari and Coeshott and their colleagues are working to identify Pluronic polymer-based formulations that stabilize vaccines from -10°C to 45°C. Their aim is to develop vaccines that are resistant to freezing and form protective matrices at elevated temperatures. Investigators are evaluating formulations based on Pluronic F127 using vaccines for measles and hepatitis B.

To maintain stability and viability, most childhood vaccines must be kept cool – both heat and freezing can ruin them. That means many must be refrigerated at the correct temperature throughout transportation, storage, and delivery. This cold chain is difficult and costly to maintain, especially in developing countries. Dr. Gardner and his colleagues are adapting high-throughput formulation technology developed by TransForm Pharmaceuticals, Inc. that can quickly screen different formulations of vaccines to identify those that are most likely to be stable, safe, and effective.