Artificial Ecology Sink As Prophylaxis Against Viral Infection
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abstract
The overall goal of the project is to create a protein-based viral prophylaxis (PVP) that will provide short-term(~2-3 months) protection against various viral infection following each intravenous infusion. This PVP approachis inspired by the ecological source-sink theory which states that the population of an organism in a landscapeis controlled by the frequency of habitats that either support (source) or do not support (sink) its populationgrowth. A population will decline towards extinction when the fraction of sink habitats in a landscape exceeds athreshold frequency. According to this source-sink theory, the spread of viral infection in the body, from a limitedlocal infection (e.g. cells directly contacting the saliva of an infected mosquito), is largely contributed by thebelow the threshold amount of sink cells (sink habitats) in the body (landscape). The central hypothesis of theproject is that the introduction of viral ‘sink’ cells in the body can act as prophylaxis against the viral infection. Inthis project, I proposed to convert host cells into artificial viral sinks by functionalizing them with PVP. Theduration of protection (2-3 months), although much shorter than that of a vaccine, will confer adequateprotection in many scenarios, such as women in the 1st trimester of pregnancy, travelers to pandemic areas,and personnel taking care of infected patients. Longer protection from PVP can be achieved through repeatedinfusion or gene therapy. In this project, I will engineer PVP against Zika virus. Successful completion of thisproject will lay the foundation of a new generation of prophylaxis against many pathogens, especially those withproven difficulty to vaccine development, such as HIV and dengue virus. In addition, unlike conventionalvaccines, which rely on the host immune system to produce the protective antibody and/or T cells, and are oftenless effective among people with weakened immune system (very old and very young, immune compromiseddue to HIV, organ transplantation, etc.), PVP will provide similar levels of protection to anyone regardless of thehealth of their immune system due to the unique protective mechanism employed by PVP.