A Public Good: Accelerating AIDS Vaccine Development
Researchers are making strides in the research and drug development necessary to combat the deadly HIV/AIDS epidemic, but more needs to be done to achieve this goal.
Published January 1, 2005
By Marilynn Larkin
Academy Contributor
More than 20 years into the HIV/AIDS epidemic, there is still no end in sight to this dreaded disease. Worse, the number of new cases of HIV/AIDS continues to climb, particularly in the less developed world.
In a presentation this July sponsored jointly by The New York Academy of Sciences’ (the Academy’s) Science Alliance and Rockefeller University’s Postdoctoral Association, Seth Berkley, founder, president, and CEO of the International AIDS Vaccine Initiative (IAVI), painted a disturbing picture of the magnitude of the epidemic, underscoring the scientific and advocacy work that needs to be done to quell it.
IAVI is a public–private partnership dedicated to putting an end to the AIDS epidemic. The organization offers financial and technical support to preventive vaccine research and development, serving as an advocate for sound public policy and as a community educator about AIDS and the clinical studies necessary to halt the disease. Scientists working with IAVI are playing vital roles in these endeavors, from basic science to regulatory issues, product management, and communicating with the media and public health officials.
“You need skill sets,” Berkley said. “But, what we really want at IAVI are people who care about the preventive vaccine issue and who are willing to dedicate themselves to trying to drive it forward. Then we match those desires with the career opportunities that are out there.”
A Two-Pronged Approach
A two-pronged approach is needed to deal with the devastation. One is to focus on the short-term emergency – preventing further spread of the virus, treating individuals who are infected, and mitigating the societal consequences. But he stressed that there also needs to be a long-term view, including creating the tools needed to end the epidemic entirely: female-controlled barrier methods and microbicides; diagnostics to improve treatment and control sexually transmitted diseases; and HIV vaccines. “A preventive vaccine is the only way we’re going to end the epidemic,” he said, “and we should settle for nothing less than ending the epidemic.”
AIDS vaccines are special in that their use would result in an international public good, Berkley emphasized. Simply put, that means the vaccine goes beyond individual protection. The message for policymakers, therefore, is that investing in HIV vaccines makes sense because it affects public health.
Several hurdles must be overcome before this potential global good becomes a global reality, however. For one thing, as drug candidates move from preclinical to phase-1 trials, success rates are low. Moreover, vaccines must be made available at low cost, which make them less attractive as investments. The result: Today’s market for vaccines is only about 1-2% of the market for pharmaceuticals. For HIV, that market is mostly in the less developed world, where companies are least likely to realize profits.
Lack of Funding
Vaccine development also is hampered by a lack of research funding. Public sector organizations – such as the National Institutes of Health in the United States, the Medical Research Council in the UK, and the ANRS [Agence Nationale de Reserche sur le Sida] in France – usually are national in their outlook and are not necessarily able to take a global view, said Berkley. Hence, the mission of IAVI: Ensure the development of a safe, effective, accessible, preventive HIV vaccine for use throughout the world.
While more than 30 HIV products are moving into trials around the world, the pipeline is duplicative. “Candidates are focused primarily on cell-mediated immunity, with little emphasis on neutralizing antibodies or mucosal vaccines. Also, the time from preclinical studies to market is far, far too slow.”
“So, here’s the take-home message,” said Berkley. “Twenty-three years into the worst viral infectious disease epidemic since the 14th century, only one vaccine candidate has been fully tested to see if it works. That is unbelievable. And with 14,000 new infections daily, speed is of the essence. We have to compress every aspect of vaccine development and access, without compromising safety.”
The challenge is to take the standard timeline, which is 35-plus years, and squeeze it down with parallel track approvals and deployment so that a safe, effective vaccine is licensed in most countries within 10 years after the start of preclinical research, with widespread access in less developed countries in less than 20 years.
Other Challenges
When a product is ultimately confirmed as efficacious, however, other challenges arise. One is pricing. What you want is to have the wealthiest nations pay the most, and the very poor pay as close to manufacturing cost as possible. “The problem here is getting wealthy country policymakers such as the United States Congress and European Union, which are focused on lowering their own domestic health care budgets, to accept that type of differential pricing.” Production poses yet another challenge. “We’ll want massive doses of the candidate produced in a timeline that allows us to immunize people at high risk, especially adolescents.”
“Advocacy, policy change, and scientific progress have to go hand in hand,” Berkley said. “Good science alone won’t get you products. Product development alone won’t get you there. You need to have it all together.”
This statement led to a discussion of how the IAVI has affected the global effort to develop an HIV vaccine. “We started out in 1994 to do something that seemed audacious in its magnitude, and yet there’s no question that we have, in fact, affected the worldwide effort. There are a lot more resources and a lot more attention being paid to a preventive vaccine. However,” he conceded, “the effort is still grossly inadequate.
“If you have a fatal disease, you’ll do anything to get treatment. But when it comes to prevention technology, there isn’t the same cry that there is for treatment.”
The Role of Advocacy
By contrast, Berkley continued, “there’s no movement for AIDS vaccines because when a mother has a child, she says, ‘my child’s not going to be bisexual. My child is never going to experiment with IV drugs.’ Nobody wants to sit there and say, ‘gee my kid may do this,’ and so there’s no advocacy for the creation of a vaccine for the next generation.”
To accomplish this, IAVI forms partnerships with organizations around the world. These organizations help IAVI staff working in their countries to build relationships, work with the media, and with the science community. Thus, for example, when you’re in Germany, you have a German group that has links, speaks the language, understands the system.” The result has been successes in countries such as India, where leaders of two opposing parties both stood up during a conference and stressed the importance of AIDS vaccines.
Does this mean the advocacy effort is a success? Yes and no. On the one hand, global spending on vaccine product development has increased from $125 million in 1994 to about $650 million in 2002. But the five-fold increase in spending is still only a “very small sliver” of HIV/AIDS spending overall, and less than 1% of total health-related R&D spending.
A Global Laboratory Network
Nonetheless, IAVI continues to have a hand in many vaccines currently in development, with more than 25 principal R&D partners working on six major vaccine projects, the Neutralizing Antibody Consortium, and human and non-human core laboratories. IAVI has also created a global laboratory network to ensure standardization of results from lab to lab. Moreover, to further compress the development timeline, IAVI is conducting trials in parallel in different countries.
The result, said Berkley, “is that we were able to bring five vaccines into the clinic in five years. The only other group that was able to do that was the Merck Corporation, which is a huge pharmaceutical company. We’ve also done clinical trials in eight countries, and shown that developing countries can be full partners in this effort. We’ve built their capacity and their leaders. We have good laboratory practices across all of our sites. We’ve done it with relatively small amounts of money, and my hope is that we’re seeing the beginning of a political movement to try to move AIDS vaccines up on the agenda.”
Also read: Antibodies, Vaccines, and Public Health
About the Author
Marilynn Larkin is a contributing editor to The Lancet.
