luminousalicorn asked:

Today I learned that vaccinia is a thing. Would you like to entertainingly describe its attributes?

Vaccinia is a less harmful relative of the Variola virus (commonly known as SMALLPOX). Not only was it important in the eradication of smallpox, but it inspired vaccines against other viruses (How Vaccination Got Its Name) so you could call it the Traitor of Viruses Everywhere.

It is a similar enough to smallpox to generate lasting immunity, which was observed when people who had been exposed to cowpox did not seem to catch smallpox. Early smallpox immunizations were given by contact with material thought to contain Vaccinia (often pus from infected cows or from the scab that formed after another person was vaccinated) but in the 1900s it was grown and kept in labs.

Although vaccinia came from cowpox, now “cowpox” generally refers to the wild virus and “vaccinia” refers to lab-grown lines. They have diverged somewhat because controlled lab conditions are very different from the wild and it has likely affected the evolution of vaccinia. Cowpox is like a feral cat and vaccinia is a pet. (Smallpox is a tiger.)

Vaccinia is not harmless! It is able to reproduce within cells, and mild illness after smallpox vaccination is common. People with eczema or immune deficiencies should not receive it. There have been attempts to make smallpox vaccines with fewer side effects by modifying vaccinia to be incapable of reproduction. (They will probably not be needed, but useful in the event of not-so-soft bioterrorism.)

Cool fact about poxviruses in general: They are DNA viruses. Most DNA viruses replicate in the nucleus and use the host machinery to transcribe their DNA to RNA. Poxviruses replicate in the cytoplasm, so they carry their own transcription machinery.

Here’s something you don’t see around anymore–smallpox is the only human infectious disease that has ever been eradicated, with the last known natural case occurring in Somalia in 1977. The virus itself still exists in two labs, one in Russia and one in the US, so there’s still stockpiles of vaccine kept around, including enough for everyone in the US due to fears of it being a potential bioterrorism agent.

The vaccine is a really interesting one in that it actually does not contain smallpox virus itself. Instead, it’s made with a much weaker but closely related virus called vaccinia. The virus is administered with a small, two-pronged (bifurcated) needle, with the vaccinator making fifteen small pokes that cause a blister to develop. After two weeks, the blister becomes a scab, and in the third week the scab falls off, leaving behind a scar.

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As you can imagine, this method of vaccinating wasn’t the easiest, so vaccinators in underdeveloped countries made extensive use of jet injectors, which were needleless and fired the vaccine into the skin through pressure. These unfortunately fell out of favor due to concern that they might become contaminated with patients’ blood–just think of what use an improved version might have among the needle-phobic population!

Vaccinia virus infections guide new vaccine designs

If we mapped out the family tree of poxviruses, then vaccinia virus (the causative agent of cowpox) and variola virus (the causative agent of smallpox) would probably be sisters. Or at the very least, cousins. This close heritage allows the relatively benign vaccinia virus to confer variola virus-protective immune responses in vaccinated individuals.

Read more at:

Image credit: Weltzin et al 2003, Nat Med 9 (9):1125-30
Safety and Immunogenicity of Novel Adenovirus Type 26– and Modified Vaccinia Ankara–Vectored Ebola Vaccines
Developing effective vaccines against Ebola virus is a global priority. In this phase 1 study of healthy volunteers, immunization with Ad26.ZEBOV or MVA-BN-Filo did not result in any vaccine-related serious adverse events. An immune response was observed after primary immunization with Ad26.ZEBOV; boosting by MVA-BN-Filo resulted in sustained elevation of specific immunity. These vaccines are being further assessed in phase 2 and 3 studies.

The first published results from a major Ebola vaccine trial in humans indicate that a new 2-part ‘prime-boost’ vaccine is safe, and could help the immune system to combat the virus. Results show that 100% of healthy adult volunteers taking part in the study achieved an initial antibody response, and this was sustained for at least eight months following prime-boost immunisation. Notably, all participants maintained Ebola-specific antibodies, while vaccine-induced T cell responses (a key marker of immunity) persisted in 77-80% of participants.

As we have learned more about the world of microbes, we have realised that it’s possible to use bacteria and viruses as treatments against disease. But although microbes often work incredibly well at protecting against infections or attacking tumours, we still don’t really know exactly how they work.

We know that our immune systems have developed ways to keep up with the devious tricks and schemes of microbes. When our cells become infected, the immune system activates a huge cascade of pathways, one of which leads to the activation of T cells against infected targets.

For T cells, forming a tight bond with these infected target cells is thought to be incredibly important in achieving a high-grade T cell killing performance.

Now, a team of scientists from the Chinese CDC has found that the tightness of the bond between a T cell and a target cell infected with vaccinia virus (administered as a therapeutic vaccine) relies heavily on the expression of the signalling molecule, MyD88. Surprisingly, it doesn’t rely much on the affinity of the T cell receptor, or the inflammatory conditions generated by the infection.

This exciting research suggests that vaccines capable of engaging the MyD88 pathway might perform better by tuning T cells to bind more tightly and kill more effectively their intended target cells.

You can find out more about this research here:

Image credit: Abcam. MyD88 staining appears in green, nuclear staining in blue and plasma membrane staining in red.