Why the coronavirus variant in South Africa hurt vaccines – and why many are still hopeful

Why the coronavirus variant in South Africa hurt vaccines – and why many are still hopeful

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But vaccine scientists and manufacturers say the data has not yet given the final say and that there is still reason to hope.

But that unpublished study included a relatively small number of young, healthy people in general. Crucially, he was unable to measure the vaccine’s effectiveness against serious illness, hospitalization or death.

Dr. Anthony Fauci said earlier that keeping people out of the hospital was “the most important thing” from a public health perspective.

“If you can prevent serious illness in a high percentage of individuals, it will greatly relieve stress, human suffering and death,” said Fauci during a call with reporters last month.

While researchers in South Africa continue to study the vaccine’s impact on hospitalization, AstraZeneca believes it will be effective against the variant when it comes to serious illness, a spokesman told CNN in a statement on Sunday.

Until more data is available, scientists are putting the puzzle together with findings from clinical and laboratory tests – each offering a different but incomplete view of how the variant may impact Covid-19 vaccines.

Clinical trials in South Africa

Prior to the AstraZeneca announcement, Johnson & Johnson and Novavax noted lower vaccine effectiveness in South Africa.

Novavax recently announced that its vaccine was 89% effective against symptomatic Covid-19 in a Phase 3 study in the UK, but appeared only 49% effective in a separate Phase 2b study conducted in South Africa. The latter increased to 60% when looking only at HIV-negative individuals.
Likewise, in the Johnson & Johnson Phase 3 study, effectiveness against moderate to severe illness differed by country: 72% in the United States versus 57% in South Africa.
The Johnson & Johnson Covid-19 vaccine is 66% effective in global testing, but 85% effective against serious illnesses, says the company

In both trials, 90 to 95% of cases in South Africa were associated with the variant, also known as B.1.351.

The positive side: the Johnson & Johnson trial showed that its single injection vaccine was indeed effective against serious illnesses in all areas.

“In all geographies, in all variants, we see 85% protection” against serious illnesses, said Dr. Mathai Mammen, the company’s global head of research and development, previously to CNN. In addition, one month after the injection, all hospitalizations and deaths occurred in the placebo group.

These Johnson & Jonhson results also raised hope for AstraZeneca.

“These two vaccines use a similar type of technology,” Dr. Shabir Madhi, a professor of vaccinology at the University of Witwatersrand in South Africa, told the BBC on Monday.

Both vaccines use another type of virus – an adenovirus – as a shell that carries genetic instructions to the human body, leading to an immune response. Johnson & Johnson uses a weakened common cold adenovirus, while AstraZeneca modified one of the chimpanzees.

“So, extrapolating this, there is still hope that the AstraZeneca vaccine can perform as well as the Johnson & Johnson vaccine in a different age group that is at risk for serious illness,” said Madhi.

Laboratory research

Although clinical tests have given a panoramic view of the vaccine’s effectiveness, laboratory research has focused on the variant’s antics at a level that is invisible to the naked eye.

Coronaviruses are known to mutate, usually in ways that are harmless to humans. But every now and then a mutation appears that makes scientists look twice. These mutations can cause changes in the peak protein – the protein that the coronavirus uses to bind to human cells and infect them. Spike protein is also an important target for antibodies that we create in response to vaccines.

A number of laboratory studies have suggested that antibodies from vaccinated people are less effective in “neutralizing” the variant of infecting cells in the laboratory. But that does not mean that the virus has escaped completely.
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Oxford’s announcement this week said that the neutralization activity against B.1.351 was “substantially reduced when compared to the original coronavirus strain.”

Similar results have been observed, albeit to varying degrees, in “almost all vaccines that have been studied against this variant in different ways, whether in the laboratory or in clinical studies”, Dr. Salim Abdool Karim, chairman of the South African government advisory panel coronavirus, previously reported to CNN.

Many laboratory studies have analyzed synthetic viruses designed to carry important mutations in B.1.351, while some research has tested the complete live virus. Experts say the latter offers a more complete picture of how mutations in the variant can interact with each other and have combined effects.
Scientists often focus on a mutation called E484K, which appears to help the variant escape some of the protection offered by the antibodies. This mutation is also part of the genetic signature of the P.1 variant initially linked to Brazil and appeared in some cases of a different variant, common in the United Kingdom.

The problem with laboratory studies, however, is that it is difficult to know whether less neutralization in the laboratory means less protection in real life.

UK coronavirus strain detects mutation that could affect vaccines, experts say

“When you look at the laboratory studies, there is less neutralizing activity against the South African strain,” vaccine expert Dr. Paul Offit told CNN after Novavax and Johnson & Johnson shared their results. These tests appear to confirm previous laboratory findings, he said.

Offit, who advises the US Food and Drug Administration on vaccines, said the two vaccines currently authorized in the U.S. – Moderna and Pfizer – may also be slightly less effective against the variant. Last year, these two vaccines showed more than 94% efficacy against symptomatic Covid-19, perhaps even more effectively against severe cases. But these results came before variants like B.1.351 were known to circulate widely.

For now, much of what we know about the effectiveness of Moderna and Pfizer against the variant comes from laboratory research. Both companies have signaled that they believe their vaccines will still protect against the variant.

“It is really difficult to compare the numbers face to face now without doing a study with two vaccines,” said Mammen of Johnson & Johnson.

Booster shots

The spotlight on antibodies, however, can leave out much of the complexity of our immune system – which can adapt to threats like the coronavirus and recruit other cells to fight, including T cells.

“You can’t see all that breadth just by looking at the antibodies,” said Marion Pepper, an associate professor in the department of immunology at the University of Washington.

Still, many of the main players are developing tools to combat variants like B.1.351, which has been found in more than 40 countries and territories around the world, including a handful of cases in the USA.

Moderna announced that it will test two separate boosters for its current two-dose regimen: an additional injection of its currently authorized vaccine and one that has been specifically modified for B.1.351. Pfizer also said it was “laying the groundwork” to create a vaccine booster.

Last month, Novavax began developing the next iterations of its vaccine, which could take the form of a booster or a “bivalent” combined vaccine. Johnson & Johnson, whose Phase 3 data came from its single vaccine, is also testing a two-dose regimen.

Similarly, Oxford and AstraZeneca are thinking about the future.

“Efforts are underway to develop a new generation of vaccines that will allow protection to be redirected to emerging variants such as booster jabs, if necessary,” said Sarah Gilbert, professor of vaccinology at the University of Oxford, said in a statement on Sunday. “We are working with AstraZeneca to optimize the pipeline needed for a voltage change, if necessary.

“This is the same problem faced by all vaccine developers, and we will continue to monitor the emergence of new variants that emerge ready for a future strain change.”

But there is no reason to expect a new generation of vaccines to receive one. On the contrary, experts say the emergence of variants makes implantation of the vaccine even more timely: the more people are vaccinated, the more hospitalizations can be avoided and the less likely the virus to mutate.

“You need to be vaccinated when it becomes available as quickly and quickly as possible across the country,” Fauci said at a virtual press conference on Monday. “Viruses cannot mutate if they don’t replicate. And if you stop replicating by vaccinating widely … you won’t have mutations.”

CNN’s Elizabeth Cohen, Jamie Gumbrecht, Jacqueline Howard, Maggie Fox and Naomi Thomas contributed to this report.

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