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The first batch of COVID vaccines touched down in South Africa in February 2021. Health workers were the first to get a jab under the Sisonke study. But even before the country had bought any jabs, our reporters were writing about the logistics and the politics of the project. If you want to know how well the vaccines work, how the different jabs compare or what it takes to create a vaccine from research, to regulation, to rollout, you’re at the right place.

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COVID crash course: A walkthrough of everything you need to know about viruses, variants and vaccines

  • Viruses adapt to survive and SARS-CoV-2 which causes COVID-19 is no different.
  • New COVID variants include surface level changes to the virus structure which means vaccines offer less protection against them.
  • But our immune system can also adapt to these different forms of the virus creating a back and forth in the fight for survival.

While half of the population of the United States has been fully vaccinated against COVID-19, South Africa has covered less than 10% of its total population, mainly as a result of not being able to procure enough jabs. Companies can simply not produce enough shots for the world’s needs, and because wealthy countries could afford to pay for vaccines before manufacturers knew how well they would work, countries like South Africa remain at the back of the queue.   

In the rest of Africa, the situation is far worse. Unlike South Africa, most governments on the continent can’t afford to buy vaccines directly from manufacturers. The only way for such countries to get shots is to buy them via the international procurement mechanism, COVAX. This means they only have access to the brands and numbers of jabs COVAX has procured. 

But hidden from the human issues of death, illness, privilege, inequity, medical science, selfishness and selflessness, is another world where immune system cells and viruses grapple mindlessly. This nanoscopic existence is a Tetris game of shapes: The correct shapes for the virus to attach to human cells and the correct shapes for immune cells to block or kill the virus.

A switch of a single amino acid (the building blocks of proteins) in a crucial spot on the SARS-CoV-2 virus spike protein on the surface of the virus can render it more infectious or invisible to antibodies, or both.

Alpha, Beta, Delta: Where did the variants come from?

Viruses succeed by making mistakes. Their existence (although there is debate about whether viruses are actually “alive”) requires constant mistakes in order to gain the advantage over their hosts (in the case of SARS-CoV-2 the host is our bodies). Errors made during replication sometimes make the new virus particles more efficient at spreading, defending themselves or replicating. Viruses with such beneficial errors thrive, while less efficient mistakes die out.

That’s how more transmissible variants of the SARS-CoV-2 virus, such as Alpha (first identified in the UK), Beta (first detected in SA) and Delta (first flagged in India and the variant that is now dominant in SA) emerged.

In addition to being more infectious than the original form of SARS-CoV-2, the Beta variant is also able to escape immunity. In other words, it has developed features which make it harder for the antibodies we develop in response to infection with the original form of the virus, as well as those we produce as a result of vaccines, to recognise and fight off the variant. In the case of the Delta variant, there is early evidence from cases in England suggesting the variant also reduces vaccine efficacy, although to a far lesser extent than the Beta variant.  

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But nothing in nature is static, and human immune cells also evolve to fight their viral foes. Antibody responses “mature”, becoming more efficient. “Both virus and antibodies are dynamically evolving systems through mutation [mistakes made in a DNA sequence as it’s being copied when the virus replicates] and selection. Both generate lots of mutations and select the best”, says Dennis Burton from the Scripps Research Institute in California. “Antibodies can distinguish your own shapes from foreign shapes.”

Evolution is a numbers game and SARS-CoV-2 now has statistics on its side even though, compared to other RNA viruses (viruses which contain RNA, molecules similar to DNA, as their genetic material) such as influenza or HIV, it is not a particularly variable virus. The reason is that SARS-CoV-2 has a proofreading component which reduces the mistakes it makes while replicating; such proofreading lowers the chances of virus-benefitting mutations occurring as well as virus-damaging mutations. 

What are viruses made of and how does the coronavirus stay alive? 

Viruses are mainly proteins (built from amino acids), nucleic acids, (chemical compounds that serve as the main information-carrying molecules in cells RNA in the case of SARS-CoV-2) and lipids (fats).

SARS-CoV-2, a coronavirus, is named for the corona, or halo, of mushroom-shaped protrusions surrounding its spherical surface. These mushrooms, or “spikes”, attach themselves to human cells.

Binding sites on the spike protein are designed to open and attach to segments of protein receptors, called ACE2 receptors, on the outside of human cells. Once the spike finds its target, the virus will fuse with the membrane of the human cell and insert its RNA to start replicating.

ACE2 receptors are found on the surface of cells and tissue, which are, for instance, present in our lungs, gut, blood vessels and heart.

The binding process works a little bit like a key being inserted into a lock, so, in effect, ACE2 is like a cellular doorway — or a receptor — for SARS-CoV-2.

Each infected person is then home to millions of replicating virus particles until their bodies have produced antibodies to kill the virus, which ups the likelihood of beneficial mistakes — for the virus at least.

How do viruses die — or fight for survival?

Fortunately for the immune system, and for vaccine makers, these receptor-binding sites on the spike protein are visible targets. Our immune systems rapidly create antibodies which lock onto these sites, and so neutralise the virus by stopping it from entering human cells and replicating. The virus-antibody pair is then cleaned up by the scavengers of the immune system, the macrophages.

Burton says: “At first SARS-CoV-2 looked to be the easiest virus in the world, the most accessible part of the receptor binding domain (RBD) stood out there. The antibody (producing) system sees it beautifully, so makes great antibodies to that part. It is very easy to induce (those antibodies) so [initially] vaccines worked spectacularly well … That’s why we got vaccines so fast, (the virus) showed this massive weakness straight off.”

Such a tempting target seems like a tactical flaw by the virus, and so it is. Temporarily at least.

But then came the SARS-CoV-2 “variants of concern”. Among the most notorious was B.1.351, now known as the Beta variant, which was identified in South Africa in late 2020. Similar strains soon appeared worldwide. The Beta variant was such an improved form of the virus that it quickly became the most commonly circulating form of the virus in South Africa. 

But Beta was only the beginning of SARS-CoV-2’s journey of survival in South Africa. In May, the most transmissible form of the virus to date, the Delta variant, was detected in the country, and it has since overtaken the Beta variant to become the primary form of the virus in South Africa. 

By the end of July, the Delta variant had spread to over 135 countries; data from England shows the AstraZeneca and Pfizer vaccines work less well against Delta than the original form of the virus. 

It is also possible that new variants could be more lethal. But Michael Gale of the Seattle-based Centre for Innate Immunity and Immune Disease and the Centre for Emerging and Re-emerging Infectious Diseases, points out it is feasible that the virus already causes the maximum amount of inflammatory responses that this type of virus can. So unless it evolves to become more directly harmful to organs, the indirect damage it can cause through triggering inflammation responses has a ceiling.  

It is, however, not unusual for some strains of a disease to be more deadly than others. Different strains of Ebola, for example, can be between 25% and 90% deadly

Ultimately, though, viruses don’t really like to kill their hosts, because they can have a much wider impact if their hosts — in the case of SARS-CoV-2 our bodies — don’t die.

How HIV vaccine research helped us to make COVID vaccines

Behind the laboratory doors, when COVID hit, scientists turned the tools they had been using to develop HIV vaccines to tackling the epidemic on their doorsteps. For example, the Johnson & Johnson vaccine uses an adenovirus 26 vector that was originally developed as an HIV vaccine and is currently being tested in South Africa in a trial known as the Imbokodo study, or HVTN705.  

A vector is a modified, harmless version of a virus (in this case an adenovirus 26) that a vaccine uses to deliver instructions to our cells to produce antibodies which can fight a specific virus (in this case SARS-CoV-2).  

Even in the case of COVID jabs such as the Pfizer and Moderna shots, products which use new mRNA technology, previous research on HIV and influenza vaccines have helped to significantly speed up the development of the shots, according to a physician-scientist, Drew Weissman, of the school of medicine at the University of Pennsylvania.  

mRNA vaccines use pieces of man-made genetic material to instruct your body to produce proteins that can fight a particular virus.

The tricks SARS-CoV-2 uses to escape antibodies

The first round of vaccines do not seem to be as potent against the new viral variants, which will continue to spawn newer strains. 

A quick response to this has been to re-engineer vaccines to target the new versions of SARS-CoV-2. This strategy can be implemented quickly and already vaccine manufacturers are working on testing altered vaccines to better match the new variants. Burton describes this as the “whack a mole approach”. “You make a new vaccine against the variant. But the virus can change again, so you whack it and it comes up somewhere else.”

There is also the added risk of original antigenic sin, where the immune system responds to an older pathogen rather than the new one. A good example, says Burton, is when people who have been infected with dengue fever then become infected with the zika virus. Their bodies focus on the original problem by making good antibodies to dengue, but bad ones to zika.

So it is possible that people who have already recovered from COVID-19 or who received one of the original vaccines will produce antibodies against the first strain virus when they should be targeting the new variant. This doesn’t necessarily make the vaccine useless, but it may make them less effective, says Burton.

“With the new variants arriving it could be that we need a yearly boost just like we do with the flu.”

There is a way to avoid this by producing broadly neutralising antibodies (antibodies which neutralise many different genetic variants of a virus) which target the conserved areas of the virus. These are parts of the virus which are so fundamental to its structure that mutations in such areas could kill it. Since these areas are so important to the survival of the virus, it has evolved over time to conceal such sites from the immune system. 

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One protective strategy used by the virus is to develop prominent decoys which trigger the immune system to make antibodies against the decoys. While the immune response is focused on these changeable areas, it is deflected from attacking more critical parts of the virus. And because these prominent areas are also more mutable, it is relatively easy for the virus to change them to escape the impact of the antibodies. 

“Usually the virus will try to hide these (conserved) sites. The virus just wants to replicate. If the virus lets the body target the conserved areas then it would die out, so they are more protected. The virus puts out the most variable parts of itself and then changes them. It is just constant mutation and selection,” says Burton.

A “universal” vaccine which would act on the more hidden conserved parts of the virus is harder to create because these areas are so well hidden. “Such ‘universal’ COVID vaccines will take longer to develop, but will work out better,” says Burton. “We possibly could make a vaccine effective against most disease-causing coronaviruses that we have seen, but you are probably looking at years rather than weeks or months.”

Will booster doses be needed to fight variants?

Simply bumping up the volume of vaccines is another strategy since all of the new variants are only somewhat better at avoiding the antibodies produced by our bodies as a result of vaccination; they are not totally immune to vaccines. Giving an extra dose of the existing vaccines could work by ratcheting up the body’s immune response so that, although less efficient, it is still able to overwhelm new variants.

This strategy is already being pursued by vaccine developers. For example, in July Pfizer-BioNTech announced they’ve “seen encouraging data in the ongoing booster trial of a third dose” of their vaccine that shows a booster dose given six months after the second dose elicits “high neutralisation titers” against both the original form of the virus and the Beta variant, which “are five to 10 times higher than after two primary doses”.

In a statement, the companies said, based on the data they had at the time, a third dose may be needed within six to 12 months after full vaccination, although the US government’s Centres for Disease Control and the country’s regulator, the Food and Drug Administration, as well as the World Health Organisation (WHO), say it’s too early to know for sure.

But countries such as Israel have already started to offer people of 60 and older who have been fully immunised with the Pfizer jab, a third booster shot. This has frustrated the WHO’s director-general, Tedros Adhanom Ghebreyesus, who has called for a moratorium on boosters until at least the end of September, to enable at least 10% of the population of every country to be vaccinated.

According to the WHO, more than 80% of the world’s COVID vaccine supply has gone to high and upper-middle-income countries, even though they account for less than half of the global population. 

Ghebreyesus said recently: “I understand the concern of all governments to protect their people from the Delta variant. But we cannot accept countries that have already used most of the global supply of vaccines using even more of it, while the world’s most vulnerable people remain unprotected.”

Belinda Beresford is an award-winning journalist and the former health and deputy news editor of the Mail & Guardian. She now lives in the United States.