The path to vaccines

This is the fourth installment in a series about COVID-19.  Here's the summary on vaccines:  If things go as well as possible, we'll have some vaccines available in the US around the beginning of 2021, they will likely require two shots, and they will probably work well enough.  Lots of people won't get the vaccine, though, so there may still be many more preventable deaths.  And the timelines could definitely be pushed to the middle of 2021.

Here is a decent FAQ-style primer with lots of links if you want deeper dives.

What is a vaccine and how does it work?

A vaccine is a medicine that, unlike most others, actually prevents you from getting sick.  The major pathway for a vaccine to achieve this is through stimulating your immune system to produce antibodies that are ready in case you are exposed in the future.  Basically, your body thinks it was already sick and is able to fight the disease off.

More specifically, vaccines usually have particles called antigens that trigger an immune response. Antigen-Presenting Cells (APCs) see them, swallow them, break them apart, and then put a piece of the antigen on their surface. This lets the quarterbacks of the immune system (T-cells) activate the antigen-specific B-cells, which directly attack the antigens through creating antigen-specific antibodies. (Some B-cells grow up to become "factories" to make a bunch of B-cells quickly, when needed.) The antibodies attach to the antigens, either directly killing them or just marking them for some grown-up T-cells to kill.

Very importantly, both B-cells and T-cells create "memory" versions so that the next time that antigen is seen, this process happens really quickly.

Here's a pic from History of Vaccines that shows all this in pretty detail.

How effective does a vaccine need to be?

A vaccine has to confer immunity to the person getting vaccinated. The term for this "immunogenicity."  A perfect vaccine would give total immunity to everyone, for all time.  Unfortunately, those don't exist; no vaccine, and for that matter no natural inoculation, is ever 100% effective for all people.  That's okay, as we aren't shooting for 100%. Just a whole bunch, for a while. Whooping cough is about 4-6 years.  Tetanus is 96% effective for 13-14 years. Those would be great.

A vaccine also has to confer immunity to the population, or the "herd." This is called the effectiveness of the vaccine once it's in the real world, or its efficacy when discussing how well it works in the lab.  

Early testing seems to indicate a COVID-19 vaccine can work.  Vaccines were already in the works for MERS and SARS, so they were not starting from scratch.  Each of the vaccines in clinical trials have neutralized the virus in the lab. (That's the "efficacy" part.) Scientists believe there would be at least a year of infection with a traditional vaccine, and likely longer, and there is hope that the newer protein-based vaccines might work much longer because they stimulate other areas of the immune system better.

What are the types of vaccines?

The 3 most common types of vaccines are weakened pathogen, dead pathogen, and pathogen subunits.  Weakened pathogens get a strong immune response, but come with more side effects. Dead pathogens have fewer side effects, but also lesser immune responses. Subunits are useful when you can find the protein or other item that causes an immune response without needing the full pathogen -- for COVID-19, that subunit is the protein "spike" that everyone talks about.

If you have to have actual pathogens, that means you have to produce actual pathogens, and that can take a lot of time.  Some subunits can be produced much more quickly.

There are a couple of other types: viral vector and nucleic acid vaccines.  Viral vectors is a newer types of vaccine that takes lab-created versions of the genetic code of the pathogens and wraps it up, a gift to the immune system wrapped in another virus so that it can get going quickly.  This has been done for Ebola, but nothing else. Nucleic acid vaccines embed the genetic code in a DNA or RNA cells directly, but act otherwise similarly to the viral vector vaccines; no nucleic acid vaccines have been approved for humans so far.  Both of these have distinct advantages to the more common types of vaccines.  First, you can use the lab and start production immediately with no need for any of the target pathogen at all.  Second, it lets the body's immune system work more naturally in certain ways.  Third, it does some interesting tracking with sugars (called glycosylation) that let's the immune system have a more accurate picture of how to recognize and fight the virus.

All of these types of vaccines are being created for COVID-19.

What vaccines are in the pipeline for COVID-19?

There are over 200 vaccines in different stages of development, with several already in Stage 3 testing (which is thousands of people).  The US government is paying the largest players to speed up the process in a plan called Operation Warp Speed, which among other results will have lots of vaccines available at no charge.

For the US, these vaccine candidates seem to be showing the most promise:

Moderna 

The Moderna vaccine because Phase 3 clinical trials in late July. It is an mRNA-style vaccine that was granted fast-track status in May.  They had positive results from animal trials, and they published positive results from Phase 1 human trials in July. The vaccine requires two doses, a month apart, and the antibody responses to the virus matched the upper quartile of people who had the disease, and the virus neutralizing aspects were in the upper half.  There were no serious side effects, but they are still working on dosing because the higher the dose, the greater the response (including the T-cell response), but also the more likelihood of fever.  

Moderna is already in production, going at risk to the tune of $750 million.  They are wanting to sell it at ~$300/person, but market prices are closer to $100/person.  But it is unclear if Americans will have to pay.

Pfizer and BioNTech

In late July, Pfizer/BioNTech have promised to deliver hundreds of millions of doses. Americans are not supposed to pay for these, which are also mRNA vaccines.  The results and side-effects were similar to Moderna's, with the best results coming from multiple doses, and the higher the dose, the better the reaction but the more likely to develop a fever.

Others

Johnson & Johnson, GlaxoSmithKline, Novavax, and Regeneron are all on their way to their own vaccines, and they have all made deals with the US government as part of Operation Warp Speed.

Outside the US

Don't forget that there are other groups outside the US.  AtraZeneca (part of Operation Warp Speed, too) seems to be one of the world contenders, using a process from Oxford, to be manufactured in China.  Sinovac, the Beijing Institute of Biological Products, and the Wuhan Institute of Biological Products are all in Phase 3 for inactivated virus vaccines. And there are a couple hundred others.

What are the timelines?

The major US companies mentioned above are already in full-scale production, and they each expect to have hundreds of millions of doses available by the end of 2020.  Assuming that they make it through FDA approval in record time, the general public should be able to start getting vaccines by early next year.  The US government has already spent a couple billion on items to be delivered by January, 2021.

If things don't go well with those, there are many others in the pipeline, including those from other countries.  It would probably be a few extra months based on production speeds and national priorities.  Remember, the whole world is working on tons of these ... but the whole world wants them, too.

Will people get them?

With any vaccine, there is a tradeoff. You are preventing yourself from getting something, but you are importantly also making it less likely for other people to be infected.  And some absolutely shouldn't get this vaccine, just like other vaccines, such as those with severely compromised immune systems.

The more people that get the vaccine, the better off everyone is.  A quarter of Americans are nervous about getting a COVID-19 vaccine.  If we only get 75% coverage, that means many more will have to be reach herd immunity.  But at that point, at least our health systems won't be in danger of being overrun, and healthcare workers and teachers will be inoculated, so the reasons to have impediments to resuming normal life will be much less.

Note that there are a lot of misconceptions about vaccines.  They are generally extremely safe and closely monitored, so here is a rare piece of advice in my early sections of this series:  Please get vaccinated as soon as they come out.  The tiny risks of the vaccine are far outweighed by the benefits.