A group of prominent vaccine researchers, including The Children’s Hospital of Philadelphia Research Institute’s chief scientific officer, Philip R. Johnson, MD, and the University of Pennsylvania’s Stanley Plotkin, MD, recently called for a “human vaccines project” to accelerate the development of vaccines to prevent “major global killers such as AIDS, tuberculosis, malaria, and other infectious diseases.”
In a Science article published May 31, the authors point out that though vaccines have been extremely effective in the past, “past strategies … are unlikely to succeed in the future,” against diseases for which there remain no vaccines. And while advances into vaccine discovery have been made, translation of those advances into successful vaccines “remains impeded by lack of understanding of key vaccinology principles in humans.” New clinical research initiatives should be established to accelerate vaccines development, the authors argue.
Wayne C. Koff, PhD, senior vice president and chief scientific officer of the International Aids Vaccine Initiative (IAVI), was the article’s first author. Other contributors include the Scripps Research Institute’s Dennis Burton, PhD, Sanofi’s senior vice president and chief scientific officer Gary J. Nabel, MD, PhD, and the Emory Vaccine Center’s Rafi Ahmed, PhD.
Past Performance Does Not Guarantee Future Results
Vaccines have “led to the eradication of smallpox, near eradication of polio, and prevention of untold millions of deaths from infectious diseases each year, and are one of the most effective public health measures available,” the authors note.
Vaccines have been responsible for marked improvements in health, quality of life, and life expectancy, but there remain many debilitating diseases for which vaccines do not exist. Chlamydia, dengue, Epstein-Barr virus, hepatitis C, herpes simplex, HIV/AIDS, malaria, rhinovirus, and tuberculosis are just some diseases that cannot be inoculated against. Many of these “cause considerable global morbidity and mortality,” the researchers point out.
For example, approximately 50-100 million people worldwide are infected with the dengue virus every year, according to the World Health Organization. Of those, 500,000 progress to the dangerous dengue hemorrhagic fever and roughly 22,000, mostly children, die. Meanwhile, malaria infects more than 200 million people worldwide, and causes approximately 660,000 deaths annually, mostly in Africa. And tuberculosis causes 8.7 million illnesses and 1.4 million deaths a year around the world.
New vaccines are clearly needed. But the development of new vaccines can be difficult, to say the least. The success rates of new vaccines are “not optimal and are even worse for the subset of complex pathogens for which viability and immune-evasion mechanisms present additional challenges,” the researchers note.
In one survey of projects cited in the Science paper, biopharmaceuticals have a 40 percent success rate compared to 22 percent for vaccines. And clinical trials of vaccines can be extremely costly — coming in between $50 and $100 million — and can take years to complete. Trials “often are undertaken with low probabilities of success,” the researchers say.
Better Vaccine Research Through Technology
But the emergence of new technologies — such as whole-genome sequencing— is “fueling a revolution in vaccine discovery,” the researchers say. Antigen discovery technologies, adjuvants (agents added to drugs to increase their effects) and delivery technologies, and next-generation sequencing technologies that will allow researchers to better decipher human immune responses offer a “tremendous opportunity for accelerating vaccine development.”
For example, antigen discovery or “reverse vaccinology” technologies allow researchers to discover antigens by sequencing whole genomes of microorganisms and using bioinformatics to design vaccines, the authors say. Likewise, researchers’ ability to “analyze immune responses at both the single cell and systems level” offers the potential to better understand how the human body responds to vaccines and to assess how protective current vaccines are.
Overall, the successful application of information made available by such new technologies could “shorten the time required for successful development of new and improved vaccines,” the researchers say. To best make use of these technological advances, and to speed the development of vaccines for diseases like dengue and malaria, they call for a “new human immunology-based clinical research initiatives” to be established.
“Collectively, such a “Human Vaccines Project” holds the potential to greatly accelerate the development of next-generation vaccines against major global killers such as AIDS, tuberculosis, malaria, and other infectious diseases; enable more successful vaccine development against allergies, autoimmune diseases, and cancers; and provide a foundation for vaccine development against new and emerging diseases,” the researchers write.
“Vaccines are the ultimate form of preventative medicine,” says CHOP’s Chief Scientific Officer, Dr. Phil Johnson. “We would much rather prevent diseases than treat them.”
“Among the most effective of public health interventions, vaccines collectively prevent the death of 2-3 million people every year. Yet researchers have not been able to devise broadly effective vaccines against a number of deadly or debilitating infectious agents that have evolved sophisticated mechanisms to evade the immune system. New approaches are needed to prevent infection by such pathogens,” said the IAVI in a statement.