Design and Engineering of Nanoparticulate Universal Vaccines

DESCRIPTION provided by applicant We have noticed anecdotally that in several of our vaccination studies certain of our andquot negativeandquot animal control groups often showed protective efficacy above what we would have expected to observe In particular andquot negative controlandquot groups of animals that contained an immunostimulatory adjuvant molecule IAM without the target antigen provided modest protection against challenge with lethal doses of viral e g influenza virus or fungal e g Aspergillus fumigatus pathogens Further the protective effect appeared to be enhanced by the presence of the cholesterol maleimide CMI moiety that is incorporated into the VesiVax r CALV conjugatable adjuvant lipid vesicles formulation to facilitate conjugation of the target antigen to the liposomes in this test group the target antigen has not been conjugated to the VesiVax r CALVs There also seemed to be a time dependence for the protective effect i e we observed that challenge with the pathogen one week after the last vaccination resulted in more effective protection than challenge three weeks or more after the last vaccination Based on these observations we designed and executed a more controlled vaccination study to examine whether or not the protective effect was real and to demonstrate that the addition of the CMI ligand enhances this effect The most thoroughly studied IAM we have tested in the VesiVax r CALV platform is monophosphoryl lipid A MPL a Toll like Receptor TLR agonist We thus used MPL as a model IAM in our preliminary studies Our results suggest that indeed significant protection from pathogen challenge can be achieved without having a target antigen present in the vaccine and that the CMI does improve the protective immune response We hypothesize that the CMI is facilitating the stimulation of protective immunity via the innate immune response Thus we propose in this SBIR Phase I application to examine the potential commercial utility of this discovery in greater detail with a goal of demonstrating that unconjugated VesiVax r CALVs have the potential to be used as a andquot universalandquot vaccine against different pathogens To maximize the impact of these studies we will test this concept in an outbred mouse model of lethal influenza challenge PUBLIC HEALTH RELEVANCE The anticipated significant outcome that will be achieved through execution of the proposed studies will be the demonstration that a VesiVax r CMI IAM formulation without a pathogen specific target antigen can stimulate potent protective immune responses against different pathogens This would be of high impact since the ability to harness the innate immune response to provide cross protection against different strains of pathogens such as influenza virus would be of great benefit to public health