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The cows are coming to save us

702 logo 702 2020-11-25

The word vaccine comes from the latin word for cow. Edward Jenner created the first vaccine using the less harmful pox virus that infected cows to infect humans and so allow them to become immune to an infection from the more serious and often deadly human version of smallpox.

He did this in a way that would horrify us today. By first infecting a young boy with cowpox he waited for him to develop the infection and then once recovered infected him with smallpox. Thankfully the boy resisted the infection. He did it to 22 more people before publishing the results of his vaccinations. That was in 1798, it would take until 1977 and a significant global effort before the World Health Organisation (WHO) could declare in 1980 that smallpox had been eradicated.

Vaccines for everything

You might think then that we should have vaccines for everything and ideally we would but viruses and bacteria did not get to be the most successful organisms without being very hard to beat themselves.

One of the greatest killers of humanity accounting for as much as half of all human deaths ever is Malaria, a parasite that gets transmitted via some mosquito species. It was identified in the 1880’s as the cause of Malaria and despite efforts to find a vaccine the first one produced was released in 2015 and despite initial efficacy the ability to prevent you becoming infected reduces over time.

Having said that the lives saved by vaccines run into billions over the years that we have had comprehensive programs to ensure our safety with global protections rising from about 20% in the 1980s to well over 80% in the last decade.

chart, timeline: Max Roser - Our World in Data © Provided by 702 Max Roser - Our World in Data

Finding a Covid-19 vaccine

Despite the Covid-19 virus being very new and there being no vaccines for any of the six prior coronaviruses that were first identified in the 1960s, there are 51 candidates undergoing testing with 10 in Phase 3 testing and three of those having provided initial results, a fourth has also declared results but not published them as yet. Never before has humanity reacted so quickly against a new virus.

This piece will focus on the three that have most recently announced their results but quite a few more are expected soon.

What must a vaccine do?

Before looking at the specific vaccines, a quick explanation about what a vaccine must do in order to be considered ready for mass use.

  • It should not harm the patient, this is the safety component. Many may have some side effects like fatigue or other symptoms that we associate with an infection because we are effectively getting the body to respond to the vaccine as if it were a new infection, but thankfully not one that could actually infect us. This is what may cause many to believe that vaccines actually make us ill. Our bodies respond to inflammation in a way to both allow us and others to know we are not well and to make it more likely we will rest, allowing the body to focus on fighting the infection. With millions of people requiring the vaccine, even a small percentage that could react negatively may translate into hundreds of people that could become more ill than had they contracted Covid-19.

  • It should be effective, a vaccine could allow you to completely resist getting infected or it may reduce the severity of the infection. Making infections less severe is still a positive outcome if severe infections could have a lasting impact or result in long hospital stays. But it may also make you asymptomatic which means you do get infected but don’t develop any symptoms and so don’t know you were infected. This too is not a bad thing but for a highly infectious virus like Covid-19, asymptomatic patients may unknowingly infect many others. Its effectiveness is also rated according to the likelihood that taking the vaccine will reduce the chance of you becoming infected if exposed. Some are as low, (flu vaccines can be a low as 405 and are often not more than 60% effective) while the best could be over 90%.

  • It should give lasting protection. The biggest drawback after having had a vaccination is one that requires you to have to get it over and over again. This does not mean it is still not useful, but it requires considerable effort to ensure everyone gets the vaccination multiple times. The seasonal flu vaccine falls into this category, getting it every year will lower the chances of you becoming infected and should reduce the time you are ill if you do become infected but you still need to get it every year. For viruses like the flu which mutate often, there is not much you can do to avoid having to keep making new vaccines as the new strains develop.

  • It should be cheap and easy to manufacture and relatively cheap and easy to transport, store and administer. Besides the economics of this, the greater challenge is whether the vaccine can be distributed to where it is needed and administered in even very challenging conditions. This is often a major stumbling block to ensure widespread application.

  • When can it be made available. Vaccines typically take at least 5 years to go through the stages of research, initial testing, reviews, approval and finally manufacture and distribution. For Covid-19 the process has been ramped up significantly allowing for the manufacturing to begin even during the testing phase on the assumption that the test will be successful and be approved. On that basis, we might see millions of doses being made available for use in the general public in just one year or less.

It is a testament to the incredible efforts and co-ordination of those tasked with fighting the virus that despite the challenges above we are able to consider the potential use of three candidates already.Two use a method that has never been approved for use in a human vaccine before.

Pfizer & Biontech

The first to publish is a two dose course taken 22 days apart. It uses messenger RNA to get your body to produce the proteins that the Sars-Cov-2 virus uses to connect and infect healthy cells via the spikes that give coronavirus its name. With your body producing just the spike proteins, your immune cells identify and remove it. Should you become exposed to the actual coronavirus the infection fighting cells will already know they can be removed and respond quicker than if you waited to become infected.

The three phases in the trial have larger and larger test groups. Phase 1 has less than a hundred participants, Phase two has less than a 1000 while the phase 3 tests have tens of thousands of participants. The Pfizer trial had 43 000 participants.

They should ideally come from a variety of backgrounds and better yet regions or countries and have a rage of age and demographic variation. It may be more risky but having participants with co-morbidities is very helpful to allowing for approval later on.

Half the participants were given the vaccine and the rest got a placebo. Pfizer asked participants to report any side effects which participants typically reported a week after the second dose. If after that point they developed covid-19 symptoms they would be tested.

Once they had 170 positive cases they unsealed the various groups and found that 162 of the positive cases were in the placebo group while 8 were in the vaccine group.

That is a very encouraging ratio.

Pfizer has agreed to make 100 million doses available to the US Government for $2 billion. That is about R600 for the two doses. South Africa has about 57 million residents which would cost about R32 billion.

Pfizer hopes to ramp up production to produce over a billion does in 2021, but the cost and the challenges of storing and transporting the vaccine suggests this will not be a likely for South Africa.

Moderna

This is also a messenger RNA virus but while the Biontech option needs to be kept at -70 Celcius for long term storage it can only last for 5 days at -3 Celcius. The Moderna vaccine is able to remain viable for a month at -3 Celcius.

It is also administered in two doses a month apart. The lengthy time between shots may allow the vaccine to be effective for longer but might not be able to prevent you becoming infected if in a region with rapidly increasing cases.

The study waited until they had 95 cases before looking to see which groups got the virus. 90 were in the placebo group and 5 were in the vaccine group. There were 11 severe cases and they were all in the placebo group.

Moderna will charge between R150 to R700 per dose which means it will cost about R300 to R1400 for the vaccine.

The cost remains an issue but the vaccine is more easily stored and transported which could make this a possible option in South Africa.

Oxford University and AstraZeneca

This one perhaps holds the greatest promise as South Africa was part of the trial and so has already worked on the protocols for administering the vaccine, but also because it can be stored at temperatures similar to other vaccines that are being used.

It also needs two doses although it what looks like a lucky oversight the doses in the UK study gave a half dose and then a full dose. Elsewhere the two doses were the same. Surprisingly the group that used the full dose in both applications had a 62% efficacy while the group that got the half dose and then the full dose were 90% effective.

The trial was stopped for a month after a participant developed a serious condition, after the investigation it was determined that the condition was not related to the vaccine and it resumed.

The vaccine uses an adenovirus found in chimps to deliver the material that will get cell to produce the spike protein. Because we have not been exposed to chimp viruses it would not be blocked by our immune system, however if it is distributed to millions for this, we would not be able to use it again as our body will detect and destroy it.

Another significant positive with this trial is that they did not wait for participants to develop symptoms before testing. They were testing during the trial regardless of symptoms, this suggests that it may not only remove symptoms but prevent you getting infected.

The best element assuming this vaccine does get approval is that Oxford made the deal with AstraZeneca that the vaccine would not be produced for profit during the pandemic. As a result a dose is expected to be about R50 which would cost South Africa a little under $6 billion.

It may prove to be very popular in which case access will be an issue, but AstraZeneca has said it plans to have three billion doses produced in the next year.

What happens next

The next big step would be that other peer reviews agree with the results obtained and that regulators approve some or all of these vaccines for use.

There are still many more being tested with candidates by Johnson and Johnson and Chinese authorities almost ready to declare results.

Despite the growing number of cases which may actually accelerate as we anticipate a vaccine, this is a very positive development, but there remains the challenge for those that don’t trust vaccines.

For the vaccine to ultimately work it needs to be administered to a large majority of the population. While the majority of people do believe vaccines are safe and effective, the challenge will be how to convince the small but significant minority that don’t trust the vaccine.

Once again, the success and failure of humanity will not be determined by nature or even a tiny virus, but by us and we can sometimes be our own worst enemy.

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