Nirvana
16-07-10, 06:02 AM
http://www.grandchallenges.org/ImproveVaccines/Challenges/NeedleFreeDelivery/Pages/NasalSpray.aspx
PRIMARY INVESTIGATOR:
Dr. James R. Baker, University of Michigan, Ann Arbor, Michigan, United States - USNanoemulsions as Adjuvants for Nasal Spray Vaccines
Nanoemulsions as Adjuvants for Nasal Spray Vaccines
http://www.grandchallenges.org/SiteCollectionImages/img_generic_project.jpgMost childhood vaccines are delivered through injection. This increases the risk that HIV, hepatitis, and other serious diseases may be transmitted by unsterile syringes and needles. Moreover, injecting vaccines can be a complex process, and used syringes and needles create a major waste disposal problem. Vaccines that can be delivered without needles have the potential to be simpler to administer and less prone to spreading infection. Some may have additional advantages over traditional vaccines, such as the ability to remain stable over a wide temperature range and to require fewer doses.
Dr. Baker's team is developing a new way of preparing vaccines so that they can be given as nasal drops. These nanoemulsion (NE)-based vaccines use non-toxic lipid droplets less than 200 nanometers in diameter that are absorbed through the mucosal surfaces of the nostrils. They can be easily produced using an extrusion process available worldwide and are antimicrobial, eliminating the need for preservatives or refrigeration. The team is performing proof-of-concept, feasibility, and toxicology studies for a nanoemulsion-based vaccine for hepatitis B surface antigen.
In addition the team continues to study the immunogenicity of the vaccine product in rats and guinea pigs. They will study the product in monkeys using the same spray device that will be used in the planned clinical trials. Investigators expect to hold a pre-investigational new drug application meeting (Pre-IND) with the U.S. Food & Drug Administration soon. The team is investigating facilities and laboratories where they will perform the GLP toxicology and GMP stability studies. Upon completion of GLP toxicology studies, investigators plan to move into a Phase I clinical trial located in the United States and Senegal.
Research Objectives:
Evaluating the induction of protective immunity in rodents and primates to ensure that the unique respiratory physiology of primates does not impose a barrier
Conducting Phase I human feasibility studies in the United States and Dakar, Senegal
BACK TO THE TOP (http://www.grandchallenges.org/ImproveVaccines/Challenges/NeedleFreeDelivery/Pages/NasalSpray.aspx#top)
Project Progress & Milestones:
In 2005-2006, Dr. Baker's team focused on formulating the vaccine adjuvant, evaluating nasal delivery devices, and demonstrating that the adjuvant, in combination with hepatitis B surface antigen, is immunogenic in mice.
In mice, the immune response to the adjuvant, W805EC, is biased toward a Th1 response. Intramuscular vaccines using alum as an adjuvant, in contrast, are biased toward Th2 response. In addition, the intranasal vaccine shows increased avidity of antibody response compared to the intramuscular vaccine with alum.
Investigators tested the vaccine product for stability at three temperatures – 40°C, 25°C, and 40°C – evaluating particle size, epitope retention, and potency at six weeks, three months, and six months.
At six weeks at all three temperatures, the NE particle size is stable, the HBsAg epitope is intact, and the vaccine product is immunogenic in mice when compared to fresh vaccine product.
At three and six months at 40°C, the NE particle size is stable, the HBsAg epitope is intact and the vaccine product is immunogenic in mice when compared to fresh vaccine product.
At three months at 25°C and 40°C, the HBsAg and NE particle size is stable and the vaccine product immunogenicity in mice is maintained when compared to fresh vaccine product.
At six months at 25°C and 40°C the NE particle size is stable but while immunogenecity is intact at 25°C, there is a decrease in immunogenicity at 40°C storage when compared to fresh vaccine product.
The decision was made to use the rat or guinea pig model in GLP toxicology studies.
PRIMARY INVESTIGATOR:
Dr. James R. Baker, University of Michigan, Ann Arbor, Michigan, United States - USNanoemulsions as Adjuvants for Nasal Spray Vaccines
Nanoemulsions as Adjuvants for Nasal Spray Vaccines
http://www.grandchallenges.org/SiteCollectionImages/img_generic_project.jpgMost childhood vaccines are delivered through injection. This increases the risk that HIV, hepatitis, and other serious diseases may be transmitted by unsterile syringes and needles. Moreover, injecting vaccines can be a complex process, and used syringes and needles create a major waste disposal problem. Vaccines that can be delivered without needles have the potential to be simpler to administer and less prone to spreading infection. Some may have additional advantages over traditional vaccines, such as the ability to remain stable over a wide temperature range and to require fewer doses.
Dr. Baker's team is developing a new way of preparing vaccines so that they can be given as nasal drops. These nanoemulsion (NE)-based vaccines use non-toxic lipid droplets less than 200 nanometers in diameter that are absorbed through the mucosal surfaces of the nostrils. They can be easily produced using an extrusion process available worldwide and are antimicrobial, eliminating the need for preservatives or refrigeration. The team is performing proof-of-concept, feasibility, and toxicology studies for a nanoemulsion-based vaccine for hepatitis B surface antigen.
In addition the team continues to study the immunogenicity of the vaccine product in rats and guinea pigs. They will study the product in monkeys using the same spray device that will be used in the planned clinical trials. Investigators expect to hold a pre-investigational new drug application meeting (Pre-IND) with the U.S. Food & Drug Administration soon. The team is investigating facilities and laboratories where they will perform the GLP toxicology and GMP stability studies. Upon completion of GLP toxicology studies, investigators plan to move into a Phase I clinical trial located in the United States and Senegal.
Research Objectives:
Evaluating the induction of protective immunity in rodents and primates to ensure that the unique respiratory physiology of primates does not impose a barrier
Conducting Phase I human feasibility studies in the United States and Dakar, Senegal
BACK TO THE TOP (http://www.grandchallenges.org/ImproveVaccines/Challenges/NeedleFreeDelivery/Pages/NasalSpray.aspx#top)
Project Progress & Milestones:
In 2005-2006, Dr. Baker's team focused on formulating the vaccine adjuvant, evaluating nasal delivery devices, and demonstrating that the adjuvant, in combination with hepatitis B surface antigen, is immunogenic in mice.
In mice, the immune response to the adjuvant, W805EC, is biased toward a Th1 response. Intramuscular vaccines using alum as an adjuvant, in contrast, are biased toward Th2 response. In addition, the intranasal vaccine shows increased avidity of antibody response compared to the intramuscular vaccine with alum.
Investigators tested the vaccine product for stability at three temperatures – 40°C, 25°C, and 40°C – evaluating particle size, epitope retention, and potency at six weeks, three months, and six months.
At six weeks at all three temperatures, the NE particle size is stable, the HBsAg epitope is intact, and the vaccine product is immunogenic in mice when compared to fresh vaccine product.
At three and six months at 40°C, the NE particle size is stable, the HBsAg epitope is intact and the vaccine product is immunogenic in mice when compared to fresh vaccine product.
At three months at 25°C and 40°C, the HBsAg and NE particle size is stable and the vaccine product immunogenicity in mice is maintained when compared to fresh vaccine product.
At six months at 25°C and 40°C the NE particle size is stable but while immunogenecity is intact at 25°C, there is a decrease in immunogenicity at 40°C storage when compared to fresh vaccine product.
The decision was made to use the rat or guinea pig model in GLP toxicology studies.