New formulation technology may ease vaccine delivery
Infants and young children in low-resource settings are particularly vulnerable to enterotoxigenic E. coli (ETEC)—bacteria that cause severe diarrhea and dehydration. ETEC leads to 300,000 to 500,000 deaths each year.* There is no approved vaccine to specifically target it; however, PATH’s enteric vaccine project
is advancing the development of ACE527, a promising candidate for the immunization of children in ETEC-endemic countries. Recently, scientists on our vaccine technologies and enteric vaccine teams partnered with Oregon Freeze Dry
to investigate a fast-dissolving tablet (FDT) technology platform as an inexpensive, scalable, and easy-to-use product presentation for the ACE527 and other vaccines.
After evaluating a series of formulations and optimizing the freeze-drying process parameters, PATH identified a lead FDT formulation with desired properties, including rapid disintegration in less than 10 seconds. This formulation has excellent storage stability at 4°C, with no appreciable loss of viability over six months. Packaged in unit-dose foil blisters that better protect the lyophilized vaccine product from moisture, the FDT may also help to reduce the overall bulk volume of vaccine during storage and transport.
FDTs can be reconstituted with a buffer, allowing the vaccine dose to be delivered to children using a liquid dropper. PATH is also exploring whether ACE527 FDTs can be designed to dissolve instantly in a small amount of saliva, eliminating the need for reconstitution. Additional assessments are underway as we continue to research the FDT technology as a value-added product presentation for a number of existing and candidate vaccines in development. For more information, please contact Dexiang Chen at dchen@path.org.
PATH scientists will present our latest findings at the 6th International Conference on Vaccines for Enteric Diseases in Cannes, France.
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PROJECT HIGHLIGHTS
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Advancing intradermal vaccine delivery with jet injectors
Intradermal (ID) delivery of some vaccines can provide full immunity using up to 80 percent less vaccine than is needed for subcutaneous or intramuscular injection. Devices that facilitate ID delivery may someday help immunization programs stretch limited vaccine supplies across a larger number of people, potentially reducing costs associated with vaccine delivery. Because accurate ID delivery with a traditional needle and syringe is difficult to ensure, PATH is researching a variety of novel delivery technologies to improve its reliability and effectiveness. One such technology is the disposable-syringe jet injector (DSJI).
In collaboration with the World Health Organization and the Global Polio Eradication Initiative, PATH and Bioject Medical Technologies
are advancing research on Bioject's ID Pen, a spring-powered needle-free jet injector, to improve the safety and ease of ID delivery for polio vaccine. PATH is also helping to demonstrate the acceptability, sustainability, and cost-effectiveness of DSJIs—plus the feasibility of using them for ID vaccine delivery—in a number of settings. In partnership with PharmaJet, our teams are pursuing research of rabies vaccine for post-exposure prophylaxis delivered intradermally. PharmaJet recently received
US Food and Drug Administration clearance for its DSJI ID delivery device, paving the way for needle-free ID delivery and product commercialization worldwide. For more information on these advancements, please contact Darin Zehrung at dzehrung@path.org.
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New tools for formulation development
Vaccine antigens, such as proteins, are structurally dynamic molecules that are sensitive to changes in temperature, oxygen, ultraviolet light, and other chemical reactions that may be initially undetectable but can accumulate over time. These and other changes in the local environment can affect the native or active conformation of the protein structure, decreasing protein stability and eventually vaccine potency. To explore these effects using structural protein characterization, PATH has purchased two new pieces of laboratory equipment: a Jasco J-815 circular dichroism (CD) spectrophotometer and a Horiba fluoromax-4 spectrofluorometer. The CD spectrophotometer monitors changes in the secondary structure and the spectrofluorometer detects changes in the tertiary and quarternary structure of proteins. Both instruments will allow our teams to observe structural changes in very dilute
samples and in samples subjected to stress conditions, including humidity and agitation. The data collected will help our scientists to rapidly identify formulations that protect vaccine antigens against a variety of environmental conditions, better enabling immunization programs to deliver fully potent vaccines.
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May 2011
IN THIS ISSUE
NEW PUBLICATIONS AND RELATED RESOURCES
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In Vaccine, PATH and partners provide a multicountry cost-model analysis of vaccination—including transport, administration, and disposal—that compares a disposable-syringe jet injector to traditional needle and syringe, both at standard depth and dose as well as reduced doses using ID delivery.
In the Bulletin of the World Health Organization PATH and partners outline the potential benefits and challenges associated with ID delivery of vaccines.
In Current Topics in Microbiology and Immunology PATH and partners examine delivery systems for ID vaccination.
A new fact sheet highlights PATH’s work in Mucosal Immunization Technologies—building on several formulation, adjuvant, and delivery technologies to potentially enable the efficient sublingual administration of subunit vaccines.
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IN THE NEWS
RECENT AND UPCOMING EVENTS
Photos, from top:
A young girl in Kenya, an ETEC-endemic country. (Richard Lord.)
PATH's fast-dissolving tablet formulation. (PATH/Patrick McKern.)
Bioject's spring-powered ID pen is small yet powerful enough to deliver injections without the use of a needle. (Bioject Medical Technologies, Inc.)
A PATH scientist explores structural changes to vaccine antigens. (PATH/Patrick McKern.)
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