The National Institute for Communicable Diseases (NICD) says levels of immunity, vaccination coverage and the impact of the 501Y.V2 mutation of the coronavirus, first identified in South Africa, are some of the key factors they are studying to determine the likelihood and severity of a third wave of coronavirus infections in the country.

Apart from population behaviour and adherence to non-pharmaceutical interventions such as the washing of hands, mask-wearing and social distancing; vaccination coverage, the NICD said, would play an important role. 

“While there is considerable uncertainty regarding many of these parameters, another resurgence of SARS-CoV-2 is likely. Predicting the timing and scale of further resurgences is, however, difficult,” the NICD said.

The co-chairperson of the Ministerial Advisory Committee on Covid-19, Professor Salim Abdool Karim, said on Sunday that South Africa was emerging from the second wave of infection with decreasing infection numbers across the board.

However, the country hit a major stumbling block last week when data from the South African trial examining the safety and efficacy of the AstraZeneca/Oxford vaccine, known as Covidshield, showed that it was not efficacious in fighting the new  501Y.V2 strain of the virus.

What vaccines will South Africa be procuring?

Apart from the one million doses of the Oxford/AstraZeneca vaccine already procured from the Serum Institute, the Minister of Health, Dr Zweli Mkhize, said the government was looking at procuring Johnson & Johnson vaccines through an implementation study, the Sputnik V vaccine from Russia, the Sinopharm vaccine from China, the Moderna vaccine from the US and also needed to explore the Novavax vaccine that is manufactured by a US company and has produced good results in a South African trial.

What vaccines are on their way to South Africa through the Covax agreement? 

The international vaccine alliance Gavi last week announced its allocation of additional doses of the Oxford/AstraZeneca vaccine as well as the Pfizer vaccine to qualifying countries, including South Africa through the Covax agreement.

Covax is the financial instrument used to pay for Covid-19 vaccines with the intention of making sufficient doses available to low and middle-income countries.

An additional 2.9 million doses will be made available to South Africa as well as 117,000 doses of the Pfizer vaccine.

What is South Africa looking for in a vaccine?

Karim said there is currently published information on four of seven clinical trials and there are three levels of evidence available to show how well vaccines work against the 501Y.V2 variant. The variant is a mutation of the original virus that made it more transmittable.

The first level was laboratory tests. Here, he said, different vaccines were seeing “diminished neutralising activity” against the 501Y.V2 variant, meaning the vaccine must produce more antibodies to kill this mutation of the virus.

The next two levels are clinical trials. He said the Johnson & Johnson vaccine provided a reduced risk of mild and moderate disease against the 501Y.V2 variant but there was no data yet on the other vaccines. 

AstraZeneca and Novavax trials have shown that clinical efficacy is diminished against the 501Y.V2 variant.

“We need the data on severe disease,” Karim added.

What are the different types of vaccines that have data to show efficacy against the coronavirus?

Some of the vaccines are using novel technology to teach the body to attack the virus’s spike protein. 

This is the part of the coronavirus that attaches to human cells. 

The messenger-RNA vaccines, Pfizer and Moderna, train the body to destroy the spike protein by using single-stranded messenger RNA. The body reads the RNA message and starts to manufacture the spike protein. This then prompts an immune response. The RNA does not alter the recipient’s DNA.

The Oxford-AstraZeneca vaccine uses a double-stranded DNA code to deliver the message.

The vector used by the Johnson & Johnson vaccine was also used successfully in vaccines for the Ebola and Zika viruses. This vaccine also uses a double-stranded DNA code and is delivered to the body by a harmless modified virus.

Researchers have been working on mRNA vaccines for the past decade to develop a vaccine against cancer.

With the Novavax vaccine, the recipient is directly injected with the spike protein and a substance that boosts the body’s immune response. This technology is also used in vaccines against whooping cough (pertussis) and diphtheria.

The Sinopharm vaccine uses an inactivated virus. This technology is also used in the polio vaccine.

More than 40 vaccines are in the human trial phase around the world at the moment.

How well are these vaccines working against the original virus and against the 501Y.V2 mutation? 

Karim said most of the vaccines worked well against the original virus. The Johnson & Johnson vaccine prevented clinically apparent Covid-19 in 66% of cases, Pfizer in 95%, Moderna in 94% and the AstraZeneca vaccine in 67%. The results looked even better for the prevention of hospitalisation and severe Covid-19. Johnson & Johnson showed 85% efficacy, Pfizer 90%, Moderna 100%, the Sinopharm vaccine 100% and the AstraZeneca/Oxford vaccine also 100%

All the vaccines showed diminished efficacy in preventing mild and moderate disease caused by the 501Y.V2 mutation. But the AstraZeneca/Oxford vaccine had the worst outcome, with only 22% efficacy. Johnson & Johnson showed 57% efficacy against the mutation and the Novavax vaccine 49%.

In laboratory tests, Pfizer showed a one- to threefold diminished efficacy, Moderna 6.4-fold and Sinopharm 1.6-fold.

What did the Oxford/AstraZeneca trial use?

The study tested the efficacy of the Oxford/AstraZeneca vaccine, known as Covidshield, on 2,000 “relatively young” healthy participants aged 18 to 65 with a median age of 31.

The main purpose of the study was to test the vaccine’s safety and to see if it would protect the recipient against Covid-19 two weeks after the second dose.

The lead investigator in the Oxford/AstraZeneca trial, Professor Shabir Madhi, said the trial was not designed to determine whether the vaccine would protect against severe Covid-19.

He said the majority of people in the trial who got sick had mild to moderate disease.

Did the vaccine work against the ‘original’ coronavirus?

Madhi explained that most of the approved vaccines currently available were designed using the original coronavirus and created antibodies with “a great affinity” for the virus’s spike protein.

When the 501Y.V2 mutation was first identified in the Eastern Cape scientists discovered that its spike protein was different from that of the original virus and as a result, the vaccines became less effective.

Madhi said the Oxford/AstraZeneca vaccine had worked very well until the end of October and data from the trial showed that those who received it had a 75% reduced risk of being infected by the original virus.

“It showed tremendous potential to prevent infection, mild and moderate disease.”

Why do the Oxford/AstraZeneca vaccine and others not work against the 501Y.V2 mutation?

Madhi explained that to ensure its survival the virus had to evade the body’s immune responses. He said they discovered through experiments done in laboratories that the antibody produced by the vaccine was not “active” against 501Y.V2. Further data in human trials showed that the vaccine only offered a 22% lower risk of infection.

What data do we still need for the Oxford/AstraZeneca trial?

Madhi said the trial data does not yet tell investigators how well the vaccine protects against severe disease, hospitalisation and death.

Will we be able to use the Oxford/AstraZeneca vaccine at all?

Madhi said several studies were underway to investigate the use of this vaccine in combination with another. In the UK, he said, investigators are looking at combining the Oxford/AstraZeneca vaccine with the Pfizer vaccine as a second dose.

“It might well be that we will explore combining the Johnson & Johnson vaccine with the Oxford/AstraZeneca vaccine in South Africa,” he said. 

Madhi said that as South Africa expected another resurgence in the winter there should be a conversation on whether the country can afford to take the risk of not vaccinating those at high risk simply because there is uncertainty whether the AstraZeneca/Oxford vaccine will protect against severe disease. 

“It will be reckless to discard a million doses of the vaccine while the probability exists that it can protect against severe disease, hospitalisation and death.”  

Karim said the “mix and match” study in the UK would provide important clues. “Given that we will be vaccinating [some] people with past immunity it bodes well, but we need empirical evidence to assess if it can be done safely,” he said.

What are the body’s killer cells and why is their response good news for South Africa?

Madhi said that the data on the body’s T-lymphocytes or killer cells gave grounds for optimism that the Oxford/AstraZeneca vaccines might protect against severe disease, hospitalisation and death due to Covid-19 

T-cells kill infected host cells and activate other immune cells and are especially important to protect against severe disease. He said the body’s T-cell response is largely unaffected by the 501Y.V2 mutation.

Why has the South African government decided to allow for an implementation study of the Johnson & Johnson vaccine?

Professor Glenda Gray, the principal investigator for the Johnson & Johnson Phase 3 Ensemble trial said their vaccine, administered as a single shot, does not protect against “the sniffles” but has a high efficacy against severe disease and death, also for the 501Y.V2 variant.

One of the strengths of the vaccine is that it was tested in a large trial of 43,783 people in the US, South America and South Africa. Around a third of the participants were older than 60, 19.6% were older than 65, 3.5% were older than 75 and 1% were older than 80. Many of the participants also had comorbidities: 28.5% were obese, 7.3% had type 2 diabetes, 10.3% had hypertension and 2.8% had HIV. Gray said the study had included others with compromised immune systems.

She said their trial was conducted at a time when infections were very high and new variants of the disease were emerging.

She said investigators saw efficacy after 14 days and an increase in immune response through to day 56 after the vaccination.

The data showed the vaccine provided high levels of protection against severe disease and hospitalisation (77% after a week and 85% after 28 days) – and it showed a 57% efficacy against the 501Y.V2 variant.

Has the vaccine been approved by Sahpra?

Gray said there is a rolling submission before the South African Health Products Regulatory Authority (Sahpra) and the investigators are adding data to it as it goes along. They have applied for emergency use of the vaccine from the US Food and Drug Administration as well as other international regulators.

What is an implementation study?

Both Gray and Karim stressed that there was an urgent need to further evaluate vaccines in large trials in South Africa to get more data.

Gray said they were in advanced negotiations to roll out the vaccine to South African health workers to evaluate its efficacy in the field.

“We can’t wait. We already have good data,” she said.

Does that mean that health workers will be guinea pigs for the vaccine?

Health Minister Mkhize has been adamant that allowing for the Johnson & Johnson vaccine to be rolled out in South Africa as part of an implementation study did not mean that doctors, nurses and other health workers would be used as “guinea pigs”.

“The vaccine has already been proven to be safe and effective. We are doing something extra. It is not the same as the original trial. We will vaccinate everyone and monitor what happens.

“We know that a single shot will stop hospitalisations and death,” Gray said. “We want to protect our healthcare workers. The quickest way to bring this vaccine to them is to use this programme.”

What about the Novavax vaccine?

Madhi is also the principal investigator in the Novavax vaccine trial. He said this trial showed that past infection with the original coronavirus did not protect against mild and moderate infections with the 501Y.V2 mutation.

However, he said this vaccine, that is a different type of vaccine from the Oxford/AstraZeneca one but was tested in a similar demographic, showed a 60% reduced risk against mild and moderate disease.

Will the existing vaccines be adapted to fight the 501Y.V2 variant?

Karim said new vaccines are being developed to accommodate this mutation.

Will the virus mutate again?

Madhi said viruses do mutate, sometimes by accident and sometimes to ensure their survival in populations where a high level of infection had occurred.

The NICD said that expert laboratories throughout South Africa are increasing their sequencing capacity and monitoring the 501Y.V2 virus in real-time.

“For example, the detection of the variant currently prevalent in the United Kingdom has now also been identified in South Africa. Ongoing mutations are expected and we expect the virus to evolve over time, the 501Y.V2 lineage to change, but also new lineages to emerge.

“Positive cases identified throughout the country are analysed daily and weekly. We review exactly these details to assess how the epidemiology of the disease is changing.

“Currently, rates of disease are stabilising or decreasing in most provinces. We will continue to monitor these data to identify any new changes or clusters of disease over the next weeks and months,” the NICD said. DM/MC

Information pertaining to Covid-19, vaccines, how to control the spread of the virus and potential treatments is ever-changing. Under the South African Disaster Management Act Regulation 11(5)(c), it is prohibited to publish information through any medium with the intention to deceive people on government measures to address Covid-19. We are therefore disabling the comment section on this article in order to protect both the commenting member and ourselves from potential liability. Should you have additional information that you think we should know, please email [email protected]

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