By all accounts the world is in dire need of a Covid-19 vaccine and it is expected that the first doses will be ready to be administered by as early as mid-December, most probably to frontline medical personnel in America.

According to reports, South Africans are likely to get a Covid-19 vaccine in the second quarter of next year, with healthcare professionals being first in line, followed by the elderly.

Over the past few months there has been much speculation on when vaccines will be ready, and how effective and accessible they will be. There has been good news of late with three pharmaceutical giants revealing that their vaccine trials are showing promising results. 

The coronavirus vaccine from Pfizer has proven to be 95% effective, while the Moderna vaccine reduced the risk of catching the virus by 94.5%. It was also announced that the Oxford vaccine showed a strong immune response in especially the elderly. The news comes as most of Europe is experiencing a second wave of the virus and local infection rates are beginning to rise.

Pfizer, together with its Covid vaccine partner BioNTech, announced last week that they have submitted a request to the US Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) of their Covid-19 vaccine candidate. 

Rajesh Narwal, a health systems adviser at the World Health Organisation (WHO) expects South Africa to see the arrival of a vaccine either in the first quarter of next year, or more likely in the second quarter. Like other countries, South Africa is set to adopt a phased approach. Stage one would see health workers prioritised and immunised, followed by the elderly. Stage two would entail 11% to 20% of the population being vaccinated, with people with comorbidities and high-priority teachers getting the shot. In stage three up to 50% of the population would be immunised, including other essential workers.

In all likelihood the vaccine will be a double-dose combination and depending on what vaccine we adopt, it is expected to cost between $1 and $3 (USD) in poorer countries, according to the WHO.

The good news for South Africa is that Johnson & Johnson (J&J) has selected Port Elizabeth-based Aspen Pharmacare as one of the companies to manufacture its Covid-19 vaccine, once it has the go-ahead for commercial production.

The vaccine candidate, Ad26.COV2-S, is currently in stage 3 of clinical trials and is one of the leading trials underway at present, involving 60 000 adults in eight countries including South Africa and the US. Indications of vaccine efficacy are expected in the first quarter of 2021. 

While the Port Elizabeth facility will be fully operational by 2023, it already has the capacity to produce more than 300 million doses of the Covid-19 vaccine candidate a year. 

The National Department of Health said that the government has put measures in place to facilitate the arrival of a vaccine. A ministerial advisory committee on the Covid-19 vaccine had been set up. There is also a National Strategy Framework, which is designed to make recommendations to the minister on funding, cost implications and other issues.

What are vaccines and how do they work?

Which vaccines are likely to be the most effective and how they work are among the questions that many people have. To answer that we first need to establish why we need a vaccine. 

Most importantly, the vast majority of people are still vulnerable to coronavirus. It is only the current restrictions that are preventing more people from dying. A vaccine would teach our bodies to fight the infection by stopping us from catching coronavirus, or at least making Covid-19 less deadly.

What vaccines are being developed and what are the differences?

Pfizer/BioNtech:

The big breakthrough came when Pfizer/BioNTech published its first results.

  • They showed it stops more than 90% of people developing Covid-19 symptoms
  • It is given in two doses, three weeks apart
  • About 43 000 people have had the vaccine, with no safety concerns

The vaccine must be stored at a temperature of around -70 degrees C and will degrade in around five days at normal refrigeration temperatures of slightly above freezing. It will be transported in a special box, packed in dry ice and installed with GPS trackers.

The vaccine is a new type called an mRNA and uses a tiny fragment of the virus’s genetic code. This starts making part of the virus inside the body, which the immune system recognises as foreign and starts to attack.

An mRNA vaccine has never been approved for use in humans, although people have received them in clinical trials for other diseases. The most important challenge for development of an mRNA vaccine remains its inherent instability because it is more likely to break apart above freezing temperatures.

Modification of the mRNA building blocks and development of the particles that can cocoon it relatively safely have helped the mRNA vaccine candidates. But this new class of vaccine still requires unprecedented freezer conditions for distribution and administration. (Read more on mRNA on www.thevillagenews.co.za.)

Pfizer said they have ramped up manufacturing capabilities across the globe in an effort to meet the high demand due to the Covid-19 pandemic. Based on current projections, the companies expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses by the end of 2021.

Moderna:

This vaccine uses the same mRNA approach as the Pfizer vaccine.

  • It protects 94.5% of people, the company says
  • It is given in two doses, four weeks apart
  • 30 000 people have been involved in the trials, with half getting the vaccine and half dummy injections

Moderna claims its vaccine can be maintained at most home or medical freezer temperatures for up to six months for shipping and longer-term storage. Moderna also claims its vaccine can remain stable at standard refrigerated conditions for up to 30 days after thawing, within the six-month shelf life.

Oxford University/AstraZeneca vaccine:

Trials of the Oxford vaccine have shown a strong immune response in older people.

  • Two weeks after a second dose, more than 99% of trial participants appeared to be protected
  • It is given in two doses
  • Trials are still continuing

This may be the easiest of the three vaccines to distribute, because it does not need to be stored at very cold temperatures. It is made from a weakened version of a common cold virus from chimpanzees, which has been modified to not grow in humans. The study shows the vaccine causes few side effects and provokes a response in T-cells that target the virus within 14 days of the first dose and a protective antibody response within 28 days of the booster dose, according to the report. Neutralising levels were achieved by 14 days after a boost vaccination in 208 of 209 recipients.

What other vaccines are being developed?

There are more than 100 vaccines being developed. Other trial results are also expected in the coming weeks.

  • Data on the Russian Sputnik V vaccine, which works like the Oxford one, suggests it is 92% efficient
  • Janssen’s trial is recruiting 30 000 volunteers worldwide, to see if two jabs give stronger and longer-lasting immunity than one
  • Wuhan Institute of Biological Products and Sinopharm in China, and Russia’s Gamaleya Research Institute are all in final testing

However, a trial in Brazil for a drug developed by the Chinese firm Sinovac was suspended after a “severe adverse incident” – believed to be a volunteer’s death.

What still needs to be done?

  • Trials must show the vaccine is safe
  • Huge-scale development must happen for the billions of potential doses
  • Regulators must approve the vaccine before it can be given
  • Researchers still need to find out how long any protection may last

It is thought that 60 – 70% of the global population must be immune to stop the virus spreading easily (herd immunity) – billions of people, even if the vaccine works perfectly.

Equally important are the unknowns about the vaccines themselves. Scientists still don’t know how long vaccine-induced protection will last, for example, or whether inoculations can block actual infection, or only prevent the onset of disease. If the latter turns out to be the case, meaning the vaccines keep us from getting sick, but not infected, we still could be infectious to others. Until we know, do not toss those masks into the trash.

What if the SARS-CoV-2 virus mutates? 

Only testing will allow data on whether the vaccine works against a mutated form of the SARS-CoV-2 virus. However, mRNA vaccine technology has the ability to be easily adapted and potentially modified relatively quickly to address new mutations of the virus. Because this technology does not include all or a portion of the actual pathogen, but instead utilises the pathogen’s genetic code, scientists could potentially modify the genetic code of the vaccine candidate to address any changes in the virus.

How do mRNA vaccines work?

Like most Covid-19 vaccine candidates, the Pfizer and Moderna vaccines are injected into the muscle, from where they enter the bloodstream and stimulate the production of antibodies to Sars-CoV-2 (specifically to the protein that forms the spikes covering its surface). 

But antibodies are only one component of the body’s adaptive immune response, which develops over time, in response to invasion by a virus or other pathogen. There is also innate immunity, which we are born with and that is mobilised instantly upon infection but is not tailored to any specific pathogen.

Vaccines train the immune system to recognize the disease-causing part of a virus. Vaccines traditionally contain either weakened viruses or purified signature proteins of the virus.

But an mRNA (also called messenger RNA) vaccine is different, because rather than having the viral protein injected, a person receives genetic material – mRNA – that encodes the viral protein. When these genetic instructions are injected into the upper arm, the muscle cells translate them to make the viral protein directly in the body.

This approach mimics what the SARS-CoV-2 does in nature – but the vaccine mRNA codes only for the critical fragment of the viral protein. This gives the immune system a preview of what the real virus looks like without causing disease. This preview gives the immune system time to design powerful antibodies that can neutralise the real virus if the individual is ever infected.

While this synthetic mRNA is genetic material, it cannot be transmitted to the next generation. After an mRNA injection, this molecule guides the protein production inside the muscle cells, which reaches peak levels for 24 to 48 hours and can last for a few more days.

Why can an mRNA vaccine be produced so fast?

Traditional vaccine development, although well studied, is very time-consuming and cannot respond instantaneously against novel pandemics such as COVID-19.

For example, for seasonal flu, it takes roughly six months from identification of the circulating influenza virus strain to produce a vaccine. The candidate flu vaccine virus is grown for about three weeks to produce a hybrid virus, which is less dangerous and better able to grow in hens’ eggs. The hybrid virus is then injected into a lot of fertilised eggs and incubated for several days to make more copies. Then the fluid containing virus is harvested from the eggs, the vaccine viruses are killed, and the viral proteins are purified over several days.

The mRNA vaccines can leapfrog the hurdles of developing traditional vaccines such as producing non-infectious viruses or producing viral proteins at medically demanding levels of purity.

mRNA vaccines eliminate much of the manufacturing process because rather than having viral proteins injected, the human body uses the instructions to manufacture viral proteins itself.

Also, mRNA molecules are far simpler than proteins. For vaccines, mRNA is manufactured by chemical rather than biological synthesis, so it is much quicker than conventional vaccines to be redesigned, scaled up and mass-produced.

In fact, within days of the genetic code of the SARS-CoV-2 virus becoming available, the mRNA code for a candidate vaccine testing was ready. What’s most attractive is that once the mRNA vaccine tools become viable, mRNA can be quickly tailored for other future pandemics.

What are the problems with mRNA?

mRNA technology isn’t new. It was shown a while back that when synthetic mRNA is injected into an animal, the cells can produce a desired protein. But the progress remained slow. That’s because mRNA is not only notoriously unstable and easy to degrade into smaller components, it is also easily destroyed by the human body’s immune defences, which makes delivering it to the target very inefficient.

But beginning in 2005, researchers figured out how to stabilise mRNA and package it into small particles to deliver it as a vaccine. The mRNA Covid-19 vaccines are expected to be the first using this technology to be approved by the FDA.

After a decade of work, the mRNA vaccines are now ready for evaluation. Physicians will be watching for unintended immune reactions, which can be both helpful and detrimental.

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