VAXFECTIN®
Vaxfectin® is a novel cationic lipid formulation optimized by us to increase the immune response to pDNA vaccines. Vaxfectin® formulations have demonstrated safety and adjuvant activity in pDNA vaccine applications in multiple animal models, including nonhuman primates. In addition, studies of Vaxfectin®-formulated pDNA vaccines against CMV and measles have shown enhanced immunogenicity in rodent and nonhuman primates, respectively. In addition, Vaxfectin® has demonstrated dose-sparing attributes as an adjuvant for protein-based influenza vaccines.
Data from a study in mice completed in 2007 showed that a seasonal influenza vaccine, sanofi pasteur’s Fluzone® commercial vaccine, formulated with Vaxfectin® generated up to 60-fold higher antibody responses than an unformulated vaccine at the same dose. Formulation of sanofi pasteur’s vaccine with Vaxfectin® also allowed a nearly 10-fold reduction in vaccine dose while generating equivalent or better antibody responses compared with unformulated vaccine, even at the lowest doses tested. In separate studies conducted by third parties, sanofi pasteur’s H5N1 pandemic influenza vaccine with no adjuvant achieved target antibody levels in less than half the subjects after two 90 mcg doses—which are six times the normal 15 mcg dose for each strain that provides 75% to 90% protection against seasonal influenza.
In a separate study in mice completed in 2007, we were able to demonstrate the potential of Vaxfectin® to be used as a dose-sparing agent with a protein-based H5N1 pandemic influenza vaccine currently stockpiled by the U.S. government. We demonstrated that after a single injection, the Vaxfectin®-formulated vaccine yielded five-fold higher antibody responses at the same dose as an unformulated vaccine, and comparable or better antibody responses at one-third the dose of unformulated vaccine. After a second injection, the Vaxfectin®-formulated vaccine yielded nine-fold higher antibody responses at the same dose as the unformulated vaccine, and five-fold better antibody responses at one-third the dose of the unformulated vaccine. Dose-sparing ability could be critical in extending limited vaccine supplies to protect the greatest number of people in the event of a pandemic influenza outbreak.
We have also completed a study which demonstrated that a measles DNA vaccine formulated with Vaxfectin® adjuvant elicited sustained protective levels of neutralizing antibodies in infant (6—10 week old) nonhuman primates confirmed by complete protection following challenge one year after intradermal vaccination, with no clinical signs of disease and no culturable virus after challenge. We found similar results in juvenile (1—2 year old) nonhuman primates. Both measles studies were conducted in collaboration with Diane E. Griffin, M.D., Ph.D., Alfred and Jill Sommer Professor and Chair of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, under a grant from the Bill and Melinda Gates Foundation. These data were published in the August issue of Clinical and Vaccine Immunology.
We also announced in August 2008 a research collaboration with the Karolinska Institutet and the Swedish Institute for Infectious Disease Control, to evaluate a Vaxfectin®-formulated preventive DNA vaccine against HIV in a Phase 1 human clinical trial as part of a prime-boost regimen. The Vaxfectin® adjuvant is intended to optimize the priming of immune responses and increase the performance of, or potentially even eliminate the need for, the viral vector vaccine boost.
We announced in November 2008 that the Naval Medical Research Center plans to conduct preclinical and Phase 1 evaluation of a dengue DNA vaccine formulated with the company’s Vaxfectin® adjuvant and delivered with the Biojector® 2000 needle-free injection system. In support of the program, we will manufacture the vaccine and the adjuvant under a $1.3 million contract, and will provide regulatory and clinical expertise.
In July 2008, we announced preliminary clinical trial data demonstrating that Vaxfectin®-formulated DNA vaccines can safely achieve significant immune responses against H5N1 pandemic influenza in humans.
In October 2008, we announced that a Vaxfectin®-formulated cancer vaccine resulted in approximately a 100-fold increase in antigen-specific CD8+ T-cell responses compared with unformulated vaccine, according to results from a mouse study reported in October. CD8+ T-cells are deployed by the immune system to identify and destroy infected or cancerous cells. We also announced data from mice studies which demonstrated that Vaxfectin®-formulated seasonal influenza vaccine generated broader, more balanced antibody responses than unformulated vaccine, and also generated influenza-specific T-cell responses. Adjusting the ratio of Vaxfectin® to vaccine drove substantial increases in either antibody or T-cell responses, without reducing the other type of response, compared with unformulated vaccine.