A number of problems plague the development of vaccines against infectious diseases, including insufficient quality and diversity of preclinical candidates, slow entry into and limited throughput in early-stage test-of-concept trials in humans, and the high cost of clinical trials. It typically takes 15 to 20 years to go from target discovery to deployment of a new vaccine even when the paradigm is well established, which is not the case for diseases such as HIV, TB, and malaria, for which new approaches are required.

A low-cost microneedle patch for delivering inactivated polio vaccine is in the testing phase.

We invest in technologies that can identify promising vaccine candidates and refine them before they enter costly and time-consuming late-stage clinical trials. We also invest in research to better understand the health factors that affect susceptibility to infectious diseases and vaccine efficacy, such as malnutrition and co-infections. Furthermore, we seek more effective models of collaboration with major vaccine manufacturers to better identify and pursue mutually beneficial opportunities.

Our vaccine discovery efforts focus on developing vaccine technologies and closing knowledge gaps to facilitate the eradication of polio, testing a new strategy for developing next-generation malaria vaccines and transmission-blocking immunotherapeutics, developing a broadly effective HIV/AIDS vaccine, and enabling more rational and accelerated development of TB vaccine candidates.

Antimicrobial drugs have been the cornerstone of infectious disease treatment, but relatively few treatment options are available for the diseases that have the greatest impact in the developing world. Drug-resistant TB and malaria are also growing problems.

We work to speed the identification of the best drug candidates, and, as we do with vaccine discovery, we look for opportunities to collaborate with pharmaceutical companies because of their unique resources and expertise and to foster productive academic-industry interactions. We also seek to develop new technologies and approaches to slow the evolution and spread of drug resistance, including alternative formulations and drug-delivery technologies.

We support efforts to create a new generation of more effective and less toxic drugs to treat malaria, TB, visceral leishmaniasis (black fever), human African trypanosomiasis (sleeping sickness), onchocerciasis (river blindness), and lymphatic filariasis (elephantiasis), and to control severe diarrhea.

A broad range of scientific studies are needed to identify how maternal, fetal, newborn, and infant health outcomes are affected by factors including nutrition, infection, and exposure to environmental toxins.

We invest in research to discover the causes of preterm birth.

We invest in research to discover the causes of preterm birth (PTB), which is a leading cause of infant mortality, and to develop innovative strategies for prevention. Efforts include developing biomarkers for PTB, which can be applied in early pregnancy to predict impending PTB and thereby target use of established preventive measures and treatments. We fund projects to establish metrics for, and discover the causes of, growth faltering in utero and during the first two years of life—a window of time in which serious health problems can impair growth and affect long-term health—and to develop new ways to prevent or reverse unhealthy growth marked by stunting and wasting. Through our Grand Challenges Explorations program and other efforts, we are seeking new approaches to measuring physical growth, brain function, and development in order to better guide and monitor healthy growth interventions.

Mosquitoes spread many serious diseases, including malaria and dengue fever, to millions of people annually. A primary strategy for fighting these diseases is the use of insecticides to kill disease-transmitting mosquitoes. Mosquitoes have grown increasingly resistant to available insecticides, however, and some insecticides are too toxic for widespread use. They also can require people to change their behavior—to use bed nets, for instance—and they need funding to maintain distribution systems.

Our investments in mosquito control include nontraditional biological and genetic approaches as well as new chemical interventions aimed at depleting or incapacitating disease-transmitting mosquito populations. One biological control project for dengue fever that began through our Grand Challenges in Global Health grant program has progressed to field trials in Australia, Indonesia, and Vietnam.

One way that we spur breakthrough advances in global health and development is through our Grand Challenges family of initiatives, which uses open requests for proposals to engage investigators across disciplines and across the world—including those who have not traditionally taken part in this type of research—to seek innovative solutions to persistent challenges.

A device under development by a U.S. company uses microneedles and vacuum suction to safely and painlessly collect blood samples for medical diagnosis.

The Grand Challenges in Global Health initiative was launched in 2003 with a focus on challenges in improving health in the developing world. We awarded 45 grants totaling more than US$450 million to scientists in 33 countries. In 2011, we began launching new programs under the initiative, and given that its scope has expanded to encompass global development, we now refer to the initiative simply as Grand Challenges.

In 2008, we launched Grand Challenges Explorations to encourage even bolder approaches in specific areas. Anyone with a great idea can apply using a simple two-page online application; no preliminary data is required. Initial grants are for US$100,000, and successful projects have the opportunity to receive a follow-on grant of up to US$1 million.

To date, more than 1,000 Grand Challenges Explorations grants have been awarded to investigators in over 50 countries, and the initiative is being used by teams across the foundation. Recent challenge topics have included new ways to measure infant brain development and gestational age and new approaches to promoting health-seeking behavior.

Governments and nongovernmental organizations around the world are developing their own Grand Challenges initiatives and committing significant funds, both independently and in partnership with the foundation. The Canadian government has funded the not-for-profit organization Grand Challenges Canada to support global health projects that integrate scientific, social, and business innovation. The U.S. Agency for International Development (USAID) has launched a series of Grand Challenges for Development programs, including Saving Lives at Birth (which includes Grand Challenges Canada and the foundation as partners) and, more recently, Fighting Ebola. We are also participating in the country-specific partnerships Grand Challenges Brazil, Grand Challenges India, and Grand Challenges South Africa.

In 2014, Bill and Melinda Gates and a diverse group of research and funding partners launched the next phase of Grand Challenges, which includes three new programs: Putting Women and Girls at the Center of Development; Creating and Measuring Integrated Solutions for Healthy Birth, Growth, and Development (part of the All Children Thriving platform); and New Interventions for Global Health.

Ethical, social, and cultural considerations are important in all of the foundation’s work. Not only do we strive to be respectful and sensitive to the communities we work with, but we also aim to design our efforts to ensure the greatest chance of acceptance, which is a prerequisite for success.

An international team of biologists is investigating ways to shorten the lifespan of mosquitoes that transmit the dengue virus.

Originally focused on supporting the Grand Challenges in Global Health initiative, our Ethical, Social, and Cultural (ESC) program now works with teams across the foundation to anticipate and address cultural barriers to global health and development initiatives. Examples of the program’s recent work include developing community engagement guidelines for tuberculosis drug trials, providing guidance for polio-related data sharing, and developing a collaboration model to promote cooperation and trust between public and private groups that work to improve infant and young child nutrition.