The proposed research will explore an entirely novel concept for design and application of a vaccine, the mutable vaccine. The mutable vaccine was conceived as an approach to attacking microorganisms like HIV and hepatitis C that mutate or change rapidly after infection, evading control by the immune system.
HIV infection does provoke an immune response but the immune response inevitably fails to eradicate HIV. The reasons immunity fails to control HIV is that HIV (and other mutator viruses) is a "moving target" - it undergoes rapid genetic changes (i.e. it mutates), creating many divergent HIV viruses, some of which lack key targets of the immune response. Moreover, even when by chance immunity potentially can attack the HIV, most HIV targets are hidden during much of the virus life cycle and over time, HIV (and hepatitis C) erodes the set of anti-virus immune cells, creating a condition of immune suppression or tolerance. The mutable vaccine overcomes these problems through several paradigm-shifting innovations. First, instead of trying to hit the "moving target" of HIV, the mutable vaccine itself mutates using some of the same pathways and at the same rate as HIV and in this way, anticipates some of the genetic changes of HIV before they happen. Second, the vaccine attaches an immune stimulator (C3d) to viral "immunogens," hastening and amplifying the immune response to viral variants. Third, the mutable vaccine accomplishes mutation and production of variants in quantity because it is put directly into specialized immune cells, called B cells, which unlike all other cells have enzymes capable of generating mutations as fast as HIV and which has apparatus that responds to inflammation and that produces and secretes large amounts of protein (in this case the viral immunogens). The mutable vaccine is inserted directly into B cells with a novel "B cell targeting vector" devised for this purpose. Fourth, the mutable vaccine platform could be readily modified to attack newly emerging infections and with modification of the approach to delivery to B cells the mutable vaccine might be considered for use in prevention of infection.
The research proposes the first testing of the mutable vaccine. The tests will be conducted in mice. We will determine how fast the vaccine mutates and how diverse are its products. The research will also determine how much immunity the mutant products generate and whether that immunity mimics the types of immunity thought potentially to control of HIV. Although the scope of the research program does not permit actual treatment of infection in non-human primates or humans, the results would offer compelling support for applications to fund such trials.
Please Note This Project Is Now Closed.
The Michigan Institute for Clinical & Health Research (MICHR) seeks innovative translational research projects that will ultimately have significant potential to improve patient and community health outcomes. The goal of this funding is to support interdisciplinary research teams in generating sufficient preliminary data to pursue future extramural funding and publication opportunities. We welcome research proposed at any stage of translation, including:
- preclinical research that aims to connect the basic science of disease with human medicine
- clinical research to better understand a disease in humans
- clinical implementation, involving the adoption of interventions demonstrated useful in the research environment into routine clinical care, and
- the study of health outcomes at the population level to determine the effects of diseases and efforts to prevent, diagnose and treat them
MICHR will fund up to five Classic Cubes ($60K) and 13 Mini Cubes ($15K).
No unit or faculty contribution is required.
Project Submission Process
Interested faculty members please provide the following information to be considered for funding:
Click the Comments tab above, and post a project idea in the Mcubed website. Please do not exceed two paragraphs in length. Provide basic details about the proposed research.
Comment should also include:
- Three cube collaborators - faculty names and units. The team must include 3 faculty from at least 2 units, and 1 faculty member on each team must be from Medicine.
- Grant amount requested ($15K or $60K)
- Studies proposing cell or animal models should provide reasoning of how the research will lead to immediate next step studies in humans.
Comments will be accepted until May 15, 2019.
Note: Project duration is one year from the transfer of funds.
For additional questions about this funding opportunity, please contact Beth LaPensee at firstname.lastname@example.org.
For eligibility requirements, use of funds, and details on the application process, please see: