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 approach
is inspired by the ecological source-sink theory which states that the population of an organism in a landscape
is controlled by the frequency of habitats that either support (source) or do not support (sink) its population
growth. A population will decline towards extinction when the fraction of sink habitats in a landscape exceeds a
threshold frequency. According to this source-sink theory, the spread of viral infection in the body, from a limited
local infection (e.g. cells directly contacting the saliva of an infected mosquito), is largely contributed by the
below the threshold amount of sink cells (sink habitats) in the body (landscape). The central hypothesis of the
project is that the introduction of viral ‘sink’ cells in the body can act as prophylaxis against the viral infection. In
this project, I proposed to convert host cells into artificial viral sinks by functionalizing them with PVP. The
duration of protection (2-3 months), although much shorter than that of a vaccine, will confer adequate
protection 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 repeated
infusion or gene therapy. In this project, I will engineer PVP against Zika virus. Successful completion of this
project will lay the foundation of a new generation of prophylaxis against many pathogens, especially those with
proven difficulty to vaccine development, such as HIV and dengue virus. In addition, unlike conventional
vaccines, which rely on the host immune system to produce the protective antibody and/or T cells, and are often
less effective among people with weakened immune system (very old and very young, immune compromised
due to HIV, organ transplantation, etc.), PVP will provide similar levels of protection to anyone regardless of the
health of their immune system due to the unique protective mechanism employed by PVP.