Vaccines to protect against infectious disease are the single most effective medical product, but developing new ones is a challenging and lengthy process, limiting their use in developing countries where they are most needed. Once a new vaccine is developed, it undergoes animal testing, which is time-consuming and does not necessarily reflect human immunity.
“It can take decades from the start of vaccine development to FDA approval at huge cost,” says Ofer Levy, MD, PhD, a physician and researcher in the Division of Infectious Diseases at Boston Children’s Hospital. “We are working on making the process faster and more affordable.”
A variety of new strategies are emerging to facilitate vaccine development and delivery:
1. Modular approaches to vaccine production
The Multiple Antigen Presenting System (MAPS) is one innovative modular method to more efficiently produce vaccines that provide robust immunity. Developed by Fan Zhang, PhD, YIngjie Lu, PhD, and Richard Malley, MD, MAPS uses the B vitamin biotin and fusions of proteins containing rhizavidin, which bind to biotin, to form a tight molecule containing both protein and sugar antigens. Such a complex offers significant immunological and technical advantages. “MAPS enables us to create a molecular complex that is more potent than the sum of its parts and triggers a stronger immune response, at a much lower cost,” says Malley.
Malley’s team is using MAPS to develop vaccines for globally important pathogens, including tuberculosis, pneumococcus and the agent of typhoid fever. “Our preliminary results show a strong immune response to our TB vaccine and protection in mice, which is very encouraging,” says Malley. The technology has been licensed to Affinivax and recently got a $4 million boost from the Bill & Melinda Gates Foundation.
2. Simulating immune systems
Using human blood cells, plasma, immune cells and other components, researchers have created the human tissue construct, an “immune system in a test tube” that can accurately simulate human immunity. Developed by Levy and fellow Boston Children’s researcher Guzman Sanchez-Schmitz, the tissue construct makes it possible to model human immune systems for different age groups, which other cellular and animal methods are unable to do. “Infections are most common in the very young and the very old,” says Levy. “Using age-specific tissue constructs, we can compare vaccine formulations to learn which may be most effective with respect to immune cells in different age groups.”
With a grant from the Boston Children’s Technology Development Fund, Levy and his team of researchers are developing a next-generation tissue construct system called the immune system unit (ISU) that will “even more faithfully reproduce the human immune system and accelerate the testing of new vaccines,” says Levy.
Such in vitro systems may be very valuable in testing and developing new adjuvants, which brings us to…
3. Boosting efficacy with adjuvants
Adjuvants are agents that are added to vaccines to boost immunity and can reduce the number of doses and the amount of antigen needed. “More effective adjuvants would reduce the amount of antigens needed for the vaccine for tremendous cost savings,” says Levy. Finding adjuvants for the influenza vaccine—which is administered to some 100 million people annually—is among the top priorities.
Boston Children’s was recently chosen by the National Institutes of Health as one of seven international sites for a $10 million Adjuvant Discovery Program. Led at Boston Children’s by Levy and David Dowling, PhD, researchers are screening about 600,000 small molecules as potential adjuvants. The screening is being conducted at Harvard Medical School, using a robotic process and testing efficacy with human tissue constructs, with the goal of finding adjuvants that “provide a broader immune response without causing inflammation and that aren’t too complicated to synthesize,” Levy says.
4. New vaccine delivery systems
Finding easier and more effective ways to administer vaccines is another active area of research. Some methods being explored include needle-free technologies such as patches, sprays and edible vaccines, which could make vaccines more palatable to children. In addition, microscopic nanoparticles, which are used in drug and cancer therapies, could serve as a transport mechanism for antigens, delivering them more directly to immune cells.
5. Increasing vaccine stability
Research is under way to develop vaccines that can better withstand hot and cold temperatures and be transported globally without losing their potency. For example, polyphosphazenes, adjuvant molecules that stabilize vaccine antigens, can be added to vaccines and dried onto microneedles for intradermal delivery. Levy’s team recently characterized polyphosphazenes’ ability to activate human newborn white blood cells, suggesting these agents may someday have utility in early-life vaccines. Another example is the use of silk to stabilize vaccines.
6. Understanding pathogenesis
“Knowledge is increasing of the mechanisms underlying infection and transmission of pathogens,” says Malley. This means that vaccines can be developed that target precise pathways that are required to cause transmission or disease. This may lead to the development of vaccines that “prevent the body from harboring organisms and prevent them from being spread or causing harm,” he says.
Elaine Gottlieb is a freelance medical writer who writes for academic medical centers and health care organizations nationwide.