By Aman Bhandari
Scientists at PATH — a Seattle-based nonprofit organization working to improve global health and well-being — have found a cheap and simple way to tackle the challenges associated with protecting hepatitis B vaccine effectiveness when the vaccine gets too hot or too cold.
Temperature regulation is one of the biggest challenges to vaccine use worldwide. According to Debra Kristensen, group leader of vaccine technologies at PATH, keeping common World Health Organization vaccines at stable temperatures requires the use of a vaccine cold chain — a global distribution network of refrigeration equipment and procedures for maintaining vaccine quality during transport and storage. Cold chain storage and exposure to extreme temperatures presents a critical obstacle to delivering needed vaccines to some of the most at-risk regions around the globe.
Other research teams in addition to PATH's are currently using various strategies to address the problem. A group of researchers at the University of Colorado at Boulder, for example, is developing a powdered, inhalable version of a measles vaccination that is ready for human testing. Innovations like these could eventually change the game, allowing for more secure and effective disease control with fewer barriers.
I recently conducted an interview with Kristensen to discuss PATH's breakthrough for the Hep B vaccine and the implications of this discovery.
Aman Bhandari: What was the primary breakthrough?
Debra Kristensen: In many parts of the world, the need to keep vaccines cold during transport and storage requires allocation of scarce resources for refrigeration equipment and special handling procedures. In addition, vaccines are frequently damaged when they are accidentally frozen or exposed to heat. Heat- and freeze-stable vaccines are more resistant to damage when temperatures rise and fall due to power outages, faulty refrigeration equipment, or handling errors.
The heat-stable hepatitis B vaccine recently developed by PATH and partners could be kept in alternate storage facilities (air-conditioned rooms) and under alternative transport conditions (insulated packaging without ice packs) for potentially its entire shelf life without compromising the effectiveness of the vaccine. The added heat stability can also facilitate outreach to remote areas.
AB: How did you get this done?
DK: PATH and partners tested many formulation approaches and perfected a particularly promising one that combines a freeze-protection method developed last year by PATH with a heat stabilization method developed by Arecor. The stabilizers used include propylene glycol — a compound that is found in many consumer products, foods and medicines, and protects the vaccine from cold—and an amino acid called histidine, which contributes to the vaccine’s heat-stabilization.
AB: Why was no one else able to do this before?
DK: To our knowledge, researchers have not previously sought solutions to protect vaccine from freeze-damage through formulation methods. The heat protection method arose out of PATH’s vaccine stabilization project to hepatitis B vaccine, which is an important childhood vaccine that is often distributed and used in difficult settings.
AB: What are the barriers to applying this technology to other vaccines?
DK: The freeze-stabilization technology is broadly applicable to vaccines containing aluminum adjuvant. PATH has placed the freeze-stabilization technology in the public domain to encourage uptake.
AB: How does this change the cost structure of delivering vaccines in general?
DK: The costs of both additives are negligible, they cost an extra one-tenth of one US penny per vaccine dose. However, the hepatitis B vaccine is a mature product that has been on the market for some time. To stabilize this vaccine now requires reformulation — plus all the necessary laboratory, preclinical, and clinical work to validate that the new product is still as effective as the existing product and also regulatory approval.
AB: On the surface this appears to be a major breakthrough. Is that how PATH scientists are viewing it?
DK: Yes, it represents a major breakthrough because this shows how we can now prevent the problem from the beginning through the vaccine formulation itself. The application of heat and freeze stabilization technologies to new vaccine products represents a sea change, of sorts, in how vaccine producers could optimize vaccine products — and, in turn, ease logistics for immunization programs as well as expand the reach and ensure the effectiveness of life-saving vaccines.
AB: Have you done projections on the increased number of vaccinations that can be done with this new technology?
DK: It is difficult to project because of the many factors that effect increases in the number of vaccinations, for example, the availability of health care workers and transportation for outreach. That said, PATH has analyzed the projected impacts of introduction of thermostable vaccines into three countries — Bangladesh, Cambodia, and Ghana. (For more information on this, please contact PATH by email at email@example.com.)
AB: Is this something that can be used in Organisation for Economic Co-operation and Development (OECD) markets?
DK: Yes, the heat and freeze stabilization technologies have the potential to optimize vaccine products for OECD markets. The challenges associated with maintaining vaccine temperature requirements during storage and transport are not limited to the developing world. No matter the country, heat/cold vaccine damage is not a simple problem — it is hard to detect. You can’t always tell whether or not a vaccine has been rendered ineffective simply by looking at it. The CDC estimates that poor refrigeration wastes hundreds of thousands of doses of vaccine every year, costing the health care system millions and, when noticed, requiring reimmunization.
Photo credit: flickr/NathanF, Creative Commons license.
Did this come about as a result of the recent bio-mimicry based developments to dry vaccines using the biological system employed by the tardigrade insect? Janine Benyus has at least two or three TED talks on this subject (ted.com) This insect temporarily dehydrates itself to survive the dry season using a very clever hack of glucose molecules. The bio-mimicry researched was specifically designed for help in transporting live viruses in a dry state (never before possible) in Africa and other places where transportation refrigeration was often an issue, but this articel mentions nothing of it...
Does anyone know? Is it an entirely separate branch of research unconnected with bio-mimicry?
I'm very interested in the chain of influence through ideas between science, media (blogs like TED and Worldchanging), industry and global issues...