Thursday, July 28, 2022

The Covid Virus Keeps Evolving. Why Haven't Vaccines?

ON MARCH 16, 2020, the first volunteer received a shot of Moderna’s then-experimental Covid-19 vaccine, just 63 days after the company had generated a genetic blueprint of the new virus. But Moderna’s rival beat it to the marketplace:

Pfizer’s Covid vaccine would be authorized for use in the United States less than a year later, a record-breaking achievement. Previously, the fastest a vaccine had ever been developed was for mumps—which took about four years.

The speed at which both companies were able to deliver their vaccines can be credited to mRNA technology. Instead of using the virus itself to spur an immune response, as older vaccines do, scientists instead spur it using a programmable piece of genetic code called mRNA. The mRNA tells the body to make a version of the coronavirus’s distinct spike protein, so it can make antibodies to neutralize that spike. The mRNA is quickly broken down, but the memory of the spike protein lingers in the immune system, so it’s ready to launch an attack if it encounters it again.

The promise of mRNA technology was its adaptability. Vaccine makers touted its plug-and-play nature. If the virus mutated to evade current vaccines, scientists could simply swap in a new piece of mRNA to match the new version of the virus. But today, despite waves of variants including Delta, Omicron, and the latest threats—Omicron subvariants BA.4 and BA.5—the Covid-19 vaccines and booster shots still target the original virus that was identified in late 2019. Why haven’t variant-specific boosters arrived sooner?

“You’re working with a virus that is rapidly mutating. Each of these variants is around for a few months and then is replaced by a new variant,” says infectious disease specialist Archana Chatterjee, dean of the Chicago Medical School. “This is a race that we are continually behind on.”

And BA.4 and BA.5 are the fastest movers yet. “This virus has, over the period of these two years, become more and more contagious,” continues Chatterjee, who is also a member of the Vaccines and Related Biological Products Advisory Committee (VRBPAC), an independent panel of experts that advises the US Food and Drug Administration.

While the currently available vaccines have greatly reduced death and hospitalization due to Covid-19, “their effectiveness does appear to wane with time,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, during a June 28 VRBPAC meeting. Initial booster shots helped restore some protection against severe disease, but their effectiveness also seems to fade.

In June, all of these factors led VRBPAC to recommend that vaccine manufacturers update Covid booster shots for fall and winter 2022, tailoring them to the BA.4 and BA.5 subvariants.

Chatterjee says the committee made the recommendation based on evidence that these subvariants seem to be driving a new wave of hospitalizations across the US and the UK. The US government intends to buy millions of variant-specific doses for a fall booster campaign.

Jacqueline Miller, senior vice president of infectious diseases at Moderna, says the company recognized early on that they’d have to race to catch up with the virus. The first variants of concern—Alpha and Beta—were identified in late 2020, just as the vaccines were being rolled out. While the original vaccines held up against the Alpha variant, they were slightly less effective against Beta. “That was really what prompted us to go down this road of investigating variant vaccines,” she says.

Miller says it takes Moderna about four to six weeks from the time of generating a new variant’s genome sequence to producing enough vaccine doses to begin human testing. Pfizer’s process is similarly fast.

“The design time to the actual production of the vaccine is still remarkably faster than other vaccines that we're talking about,” says Michael Diamond, a viral immunologist at Washington University in St. Louis who has studied mRNA vaccines. “The variants are just coming faster than we anticipated.”

The late-2020 Beta variant was quickly supplanted by Delta, which took hold in summer 2021 and caused another surge of infections around the world. Both Moderna and Pfizer rushed to test updated shots aimed at the Delta variant. But the companies' original vaccine formulas proved effective against Delta because its spike protein wasn’t all that different from the ancestral version of the virus.

When Omicron emerged in November, it had dozens of mutations in its spike protein that allowed it to more easily escape the vaccine. It caused an explosion in Covid cases over the following months.

While the process of updating an mRNA booster goes rather quickly, testing and manufacturing it at scale takes longer. Variant-specific vaccines still need to go through animal and human testing to make sure they’re safe and generate an immune response. The FDA has said that vaccine makers can bypass large trials for updated Covid vaccines and instead test them in smaller groups of volunteers, similar to what’s done for the annual flu vaccine.

Then, companies need to study volunteers’ blood to compare the immune response generated by the modified booster to the one generated by the original vaccine. The whole process from start to finish takes Moderna about six months, says Miller.

And that’s not counting the time it takes for FDA authorization, to make the new formula, or to get it to pharmacies and doctor's offices. Miller says she hopes the timeline will get shorter once the first variant-specific booster is out of the gate.


Pair of new studies point to natural Covid-19 origin

An animal market in China’s Wuhan really was the epicentre of the Covid pandemic, according to a pair of new studies in the journal Science published overnight Tuesday that claimed to have tipped the balance in the debate about the virus’ origins.

Answering the question of whether the disease spilled over naturally from animals to humans, or was the result of a lab accident, is viewed as vital to averting the next pandemic and saving millions of lives.

The first paper analysed the geographic pattern of Covid cases in the outbreak’s first month, December 2019, showing the first cases were tightly clustered around the Huanan Market. The second examined genomic data from the earliest cases to study the virus’ early evolution, concluding it was unlikely the coronavirus circulated widely in humans prior to November 2019. Both were previously posted as “preprints” but have now been vetted by scientific peer review and appear in a journal.

Michael Worobey of the University of Arizona, who co-authored both papers, had previously called on the scientific community in a letter to be more open to the idea that the virus was the result of a lab leak. But the findings moved him “to the point where now I also think it’s just not plausible that this virus was introduced any other way than through the wildlife trade at the Wuhan market,” he said on a call about the findings.

Though past investigation had centred on the live animal market, researchers wanted more evidence to determine it was really the progenitor of the outbreak, as opposed to an amplifier. This required neighbourhood-level study within Wuhan to be more certain the virus was “zoonotic” – that it jumped from animals to people.

The first study’s team used mapping tools to determine the location of most of the first 174 cases identified by the World Health Organisation, finding 155 of them were in Wuhan.

Further, these cases clustered tightly around the market – and some early patients with no recent history of visiting the market lived very close to it. Mammals now known to be infectable with the virus – including red foxes, hog badgers and raccoon dogs, were all sold live in the market, the team showed. The study authors also tied positive samples from patients in early 2020 to the western portion of the market, which sold live or freshly butchered animals in late 2019.

The tightly confined early cases contrasted with how it radiated throughout the rest of the city by January and February, which the researchers confirmed by drilling into social media check-in data from the Weibo app. “This tells us the virus was not circulating cryptically,” Professor Worobey said. “It really originated at that market and spread out from there.”

The second study focused on resolving an apparent discrepancy in the virus’ early evolution. Two lineages, A and B, marked the early pandemic. But while A was closer to the virus found in bats, suggesting the coronavirus in humans came from this source and that A gave rise to B, it was B that was found to be far more present around the market.

The researchers used a technique called “molecular clock analysis,” which relies on the rate at which genetic mutations occur over time to reconstruct a timeline of evolution – and found it unlikely that A gave rise to B. “Otherwise, lineage A would have had to have been evolving in slow motion compared to the lineage B virus, which just doesn’t make biological sense,” Professor Worobey said.

Instead, the probable scenario was that both jumped from animals at the market to humans on separate occasions, in November and December 2019. The researchers concluded it was unlikely that there was human circulation prior to November 2019. Under this scenario, there were probably other animal-to-human transmissions at the market that failed to manifest as Covid cases.

“Have we disproven the lab leak theory? No, we have not. Will we ever be able to know? No,” said co-author Kristian Anderson of The Scripps Research Institute. “But I think what’s really important here is that there are possible scenarios and they’re plausible scenarios and it’s really important to understand that possible does not mean equally likely.”




1 comment:

Anonymous said...

Are the new variants of COVID still as dangerous as the previous variants?

That is the question I can't seem to get an answer to. I haven't heard of how many people are dying from COVID in quite some time, I haven't heard on anyone I know dying from COVID in nearly a year now.

Are we making a lot of news about what is now effectively just another variant of the common cold?