Completed Infection & Immunity Cancer

Vaccinia virus entry, exit and evasion

In plain English

AI plain-English summary

Vaccinia virus, the live vaccine that eradicated smallpox, is still actively dismantling human immune defences in laboratories today. This research tracks exactly how the virus breaks into cells, builds new copies of itself, and then evades the immune system to spread to neighbouring cells. Understanding these mechanisms matters because vaccinia virus is now being repurposed as a vaccine platform for other infectious diseases and for cancer. The problem is that the current virus can cause serious side effects in people with weakened immune systems, and it does not always trigger a strong enough immune response. Without knowing precisely how the virus enters and exits cells, or how it dodges immune detection, engineers cannot reliably redesign it to be both safer and more effective. If this research succeeds, it will provide the molecular blueprint needed to engineer vaccinia virus into a more predictable vaccine vehicle. This is fundamental science with a clear downstream application: a safer, more immunogenic vaccine platform that could be deployed against emerging infectious threats or used to train the immune system to attack tumours.

View original technical description
Viruses remain a potent threat to human health as illustrated by the current epidemics caused by influenza virus and human immunodeficiency virus. Basic research on how viruses replicate, spread and evade our immunological defences is important in advancing our understanding of how viruses cause disease and will underpin the development of new vaccines and anti-viral drugs. This proposal concerns vaccinia virus (VACV), a poxvirus and the live vaccine that was used to eradicate smallpox. Although smallpox has been eradicated, VACV continues to be studied because i) it is possible to engineer VACV as a vaccine against other infectious diseases, and ii) the interaction between VACV and the host cell and immune system is providing novel, fundamental information about how viruses cause disease. This application will focus on how VACV enters cells, how new virus particles are transported out of the cell, how these virus particles spread rapidly to other cells, and how VACV evades the immune response to infection. The information obtained will facilitate the engineering of VACV as a safer and more immunogenic vaccine for infectious diseases and cancer.

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Researchers

Geoffrey Smith (Principal Investigator)

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Original classification

Research Grant

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