Why South Africa’s Coronavirus Variant Has Put Vaccines Under Pressure – And Why Many Are Still Hopeful

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But scientists and vaccine makers say the data doesn’t have the final say yet, and there’s still reason to be hopeful.

But that unpublished study involved a relatively small number of people who were generally young and healthy. Crucially, it could not measure how effective the vaccine was against serious illness, hospitalization, or death.

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

“If you can prevent serious illness in a high percentage of people, it will alleviate so much of the stress and human suffering and death,” Fauci said during a phone call with reporters last month.

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

Until more data becomes available, scientists are putting the puzzle together with findings from clinical trials and the lab – each with a different but incomplete picture of how the variant might affect the Covid-19 vaccines.

Clinical Trials in South Africa

Before the AstraZeneca announcement, both Johnson & Johnson and Novavax had seen lower vaccine efficacy 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 it was found to be only 49% effective in a separate Phase 2b study conducted in South Africa. The latter increased to 60% when only HIV-negative persons were considered.
Similarly, in Johnson & Johnson’s Phase 3 trial, efficacy against moderate to severe disease differed by country: 72% in the US versus 57% in South Africa.
Johnson & Johnson Covid-19 vaccine is 66% effective in global studies, but 85% effective against serious diseases, company says

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

The Silver Lining: The Johnson & Johnson study showed that the one-time vaccine was indeed effective against serious illness across the board.

“In all geographic areas, in all variants, we see 85% protection” against serious diseases, said Dr. Mathai Mammen, the company’s global head of research and development, previously at CNN. In addition, from one month after the injection, all hospital admissions and deaths occurred in the placebo group.

These results from Johnson & Jonhson have also given hope for AstraZeneca.

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

Both vaccines use a different type of virus – an adenovirus – as a shell that carries genetic instructions into the human body, triggering an immune response. Johnson & Johnson uses an attenuated cold adenovirus, while AstraZeneca adapted one from chimpanzees.

“So I think if I extrapolate from that, there is still some hope that the AstraZeneca vaccine will perform as well as the Johnson & Johnson vaccine in another age group at risk of serious disease,” said Madhi.

Research in the lab

While clinical studies have given a bird’s-eye view of vaccine efficacy, laboratory research has focused on the mischief of the variant at levels invisible to the naked eye.

Coronaviruses are known to mutate, generally in ways that are harmless to humans. But every now and then a mutation pops up that makes scientists look twice. These mutations can cause changes in the spike protein – the protein that the coronavirus uses to attach to and infect human cells. The spike protein is also a major target of the antibodies we make in response to vaccines.

A number of laboratory studies have suggested that antibodies from vaccinated humans are less effective at “neutralizing” the variant of infecting cells in the laboratory. But that doesn’t mean the virus has escaped completely.
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Oxford’s announcement this week stated that neutralization activity against B.1.351 was “significantly reduced compared to the original coronavirus strain.”

Similar results have been seen, albeit to varying degrees, with “almost all vaccines that have been differently studied against this variant, either in the laboratory or in clinical studies,” says Dr. Salim Abdool Karim, the chair of the South African government’s coronavirus advisory panel, previously told CNN.

Many laboratory studies have looked at synthetic viruses designed to carry key mutations in B.1.351, while some studies have tested the whole live virus. Experts say the latter offers a more complete picture of how the variant’s mutations can interact with each other and have combined effects.
Scientists have often focused on a mutation called E484K, which appears to help the variant escape some of the protection provided by antibodies. This mutation is also part of the genetic signature of the P.1 variant that was first linked to Brazil, and has shown up in a handful of cases of another variant common in the UK.

The problem with lab studies, however, is that it’s hard to know if less neutralization in the lab means less protection in real life.

Coronavirus strain in the UK is picking up mutations that can affect vaccines, experts say

“If you look at the studies done in labs, there was less neutralizing activity against the South African strain,” said vaccine expert Dr. Paul Offit to CNN after Novavax and Johnson & Johnson shared their results. Those tests seemed to confirm previous lab findings, he said.

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

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

“It’s really hard to compare the numbers right now without doing a study with two vaccines,” said Mammen of Johnson & Johnson.

Booster shots

However, the spotlight on antibodies can omit much of the complexity of our immune system – which can adapt to threats like the coronavirus and recruit other cells for battle, including T cells.

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

Still, many of the major players are developing tools to combat variants such as B.1.351, which have been found in more than 40 countries and territories around the world, including a handful of cases in the US.

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

Last month, Novavax began development of the next iterations of its vaccine, which can be in the form of a booster or a combined “bivalent” vaccine. Johnson & Johnson, whose Phase 3 data came from the single vaccine, is also testing a two-step treatment.

Likewise, Oxford and AstraZeneca are thinking ahead.

“Efforts are underway to develop a new generation of vaccines that can divert protection to emerging variants such as booster jabs when the need arises,” said Sarah Gilbert, professor of vaccinology at Oxford University. said in a statement Sunday. “We are working with AstraZeneca to optimize the pipeline required for a change of rack, should the need arise.

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

But there is no reason to wait for a new generation of vaccines to get one. On the contrary, experts say the emergence of variants makes the vaccine rollout all the faster: the more people vaccinated, the more hospital admissions can be prevented, and the less likely the virus is to mutate.

“You should get vaccinated if it becomes available nationwide as soon as possible,” Fauci said in a virtual newsletter Monday. “Viruses cannot mutate if they don’t replicate. And if you stop their replication by vaccinating on a large scale … you don’t get mutations.”

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

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