MOLECULAR EXPRESS, INC — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant The principal objective of this proposal is to develop an Aspergillus fumigatus VesiVax r vaccine The studies proposed in this Phase I Application will specifically address refining a liposomal based vaccine using the defined candidate antigens i e Aspf Aspf and AspfHemolysin that will provide protective immune responses against aspergillosis Our central hypothesis is that a highly immunogenic liposome delivery system developed by Molecular Express VesiVax r can be used to rapidly design and engineer candidate vaccines against A fumigatus The liposomal Aspergillus vaccine candidates will be tested in a relevant immunocompromised mouse model for their ability to protect against a pulmonary Aspergillus challenge Preliminary data using Aspf Aspf and Aspf Hemolysin are very encouraging Here we intend to follow up those studies by determining the minimum number of Aspf proteins needed for the vaccine and the dosage of vaccine that is optimal We will also determine whether the Aspf vaccine will provide additional protection to animals requiring antifungal therapy It is conceivable that A fumigatus may break through the host immunity in vaccinated patients that are also immunocompromised e g patients on chemotherapy We will test whether the Aspf vaccination prior to infection can ameliorate the fungal infection when antifungal therapy is used post infection We will determine the colony forming units in the lungs bronchial alveolar lavage BAL and kidneys to assess the extent of Aspergillus fungal infection In addition to survival and signs of disease we will measure cytokine levels in the BAL and lungs to determine if there is a decrease of inflammatory cytokines in the BAL and lung tissue in infected mice Histopathological analysis will be done on the lungs to determine the level of fungal infection and the type and extent of the immune response in these tissues From these studies described in this SBIR Phase I application the most effective candidate Aspergillus vaccine candidate will be used for advancement to clinical evaluation and development of a commercial product Commercialization will be done with the intent of using our Aspf vaccine to prevent or ameliorate disease in the primary patient population the immunocompromised hosts such as those individuals undergoing a solid organ transplant bone marrow transplant or cancer chemotherapy In these patients the opportunity exists to immunize the patient prior to the onset of the most severe immunosuppression with the goal that the acquired resistance from the vaccine can carry over through the course of the immunosuppression thus reducing patient mortality and infection with Aspergillus PUBLIC HEALTH RELEVANCE The principal objective of this proposal is to develop an Aspergillus fumigatus vaccine We have previously published data showing that our liposomal based vaccines can stimulate a strong protective immune response against influenza and Herpes Simplex Virus We have preliminary data showing that the use of three Aspergillus proteins incorporated into the VesiVax r liposome formulation also stimulates a protective immune response in both a systemic and pulmonary A fumigatus mouse model Here we propose to further evaluate these A fumigatus protein vaccines to identify the best combination and dose We will further evaluate the added value of this Aspergillus vaccine in conjunction with antifungal therapy in an immunocompromised pulmonary aspergillosis mouse model From these studies we will identify a candidate A fumigatus vaccine that will be further evaluated for efficacy against other Aspergillus species and to develop this into a commercial vaccine product