Thread by @peripatetical

A thread about the SARS-CoV-2 vaccines in development. There are a lot of candidate vaccines in development, but we still have a long way to go.

Vaccines work by training the immune system on a virus or a component that doesn't cause disease, so that it can respond more efficiently when it sees the real thing.

For SARS2, there are many different approaches being tried. These can be classed into 4 main groups - inactivated/live attenuated, protein subunits, viral vectors and nucleic acid vaccines.

The LSHTM website is tracking more than 200 candidate vaccines under development. Of these, 25 are being tested in humans
vac-lshtm.shinyapps.io/ncov_vaccine_l…

Inactivated and live attenuated vaccines are the traditional tried-and-true vaccines. Examples include influenza (inactivated) and measles (live attenuated) vaccines.

Four inactivated vaccines are in phase 1/2 trials, all manufactured by Chinese companies. Some of these have shown promise in primate studies and are entering human studies
science.sciencemag.org/content/369/64…
news-medical.net/news/20200626/…

Protein subunit vaccines are made by using a viral component. An example is hepatitis B vaccine, made from the surface antigen of the virus without the other viral machinery that make it infect humans.

For SARS2, the candidates are mostly based on the spike protein, or a small part of this protein called the receptor binding domain. These vaccines will probably require adjuvants, or substances that attract and stimulate immune responses at the site of vaccination.

Several candidates are in human trials, including the Novavax vaccine NVX-CoV2373 that appears to be protective in animal studies, being tested in Australian sites
biorxiv.org/content/10.110…

The UQ vaccine is another example of this vaccine type
thenewdaily.com.au/news/coronavir…

As is the COVAX-19 candidate developed by Vaxine at Flinders University
abc.net.au/news/2020-07-0…

Viral vector vaccines are relatively new and combine a harmless virus with a component of the virus of interest. Examples include the Ebola vaccine (based on vesicular stomatitis virus) and Dengvaxia (based on the yellow fever vaccine strain).

For SARS2, two vaccine candidates that are showing promise are the Oxford ChAdOx1 vaccine (based on chimpanzee adenovirus) and the CanSino adenovirus 5 vaccine.

The Oxford vaccine seemed to provide possible protection in primates - although they still got infected (after being challenged with a high dose of SARS2), they didn't get pneumonia
biorxiv.org/content/10.110…

The Chinese vaccine, based on human adenovirus type 5 stimulated the immune system to make neutralising antibodies.
thelancet.com/journals/lance…

A potential issue with these vaccines is that prior infection with adenovirus may impair immune responses to SARS2 antigens. This may also mean that any subsequent dose may not be effective.

The nucleic acid vaccines haven't been used in any currently available human vaccine. They work by introducing genetic codes (RNA or DNA) for a viral protein, which is taken up into cells. This is translated into the protein by cells, stimulating an immune response.

The Moderna mRNA vaccine is one of several candidates in this group. Results published yesterday suggest that the vaccine induced antibodies that could neutralise the virus
nejm.org/doi/full/10.10…

The accompanying editorial notes many difficult decisions that will need to be made. This will apply to all vaccines in development.

Some unknowns - the dose that elicits antibodies without excessive side effects (may be different in younger and older people). Whether antibodies are protective. Where to do the final trial. What the endpoint should be (infection or severe infection)
nejm.org/doi/full/10.10…

There are many hurdles to go before we get an effective vaccine. The lead candidates may not turn out to be protective, or may have intolerable side effects. But in this crowded field, we'd be hopeful that at least one will be successful.

There are many steps after this - demonstrating quality, safety and efficacy to regulators, producing billions of doses, making sure they are distributed equitably, and making sure that people are happy to get the vaccine.

The speed that we've got to this point is breathtaking - the editorial notes that 6 years of work has been compressed into 6 months. But we still have a long way to go.