Chicago – After developing and rolling out COVID-19 vaccines at record speed, drugmakers are already facing variants of the rapidly-evolving coronavirus that may render them ineffective, a challenge that will require months of research and a massive financial investment, according to disease experts.
Executives from Moderna Inc. and Pfizer Inc. and partner BioNTech SE are considering new versions of their vaccines to respond to the most concerning variants identified so far. That is just one piece of the work needed to stay ahead of the virus, nearly a dozen experts said.
A global surveillance network to assess emerging variants must be built. Scientists need to establish what level of antibodies will be required to protect people from COVID-19 and determine when vaccines need to be altered. And regulators must convey what is needed to demonstrate updated vaccines are still safe and effective.
“At this point, there is no evidence that these variants have changed the equation in terms of protection from the vaccine,” said Dr. Michael Osterholm, an infectious disease expert at the University of Minnesota. “But we have to be prepared for that.”
Johnson & Johnson said the concerning variant first identified in South Africa has got its attention and will tweak its vaccine accordingly if needed. Pfizer said it could produce a new vaccine relatively quickly, but a top vaccine executive said manufacturing it presents additional challenges. Novavax Inc. said Thursday its coronavirus vaccine was 89.3% effective in preventing COVID-19 in a trial conducted in the United Kingdom, and was nearly as effective in protecting against the more highly contagious variant first discovered in the UK, according to a preliminary analysis. A mid-stage trial of the vaccine in South Africa, where a potent variant of the virus is common, showed 60% effectiveness among people who did not have HIV.
The urgency of this effort by drugmakers is clear. State health officials in South Carolina on Thursday reported the first two cases of the South African variant in the United States.
Moderna on Monday said lab studies showed antibodies made in response to its vaccine were six times less effective at neutralizing a lab-created version of a South African variant than prior versions of the virus.
A study released prior to a peer review on Wednesday found the South African variant reduced neutralizing antibodies by 8.6 times for the Moderna vaccine and by 6.5 times for the Pfizer/BioNTech shot, although a separate Pfizer-backed study released on Wednesday suggests its vaccine may be more hardy. Moderna said this week it is starting work on a potential booster shot.
Just how far protection can drop before a COVID-19 vaccine needs to be altered is not yet known. With influenza, an eightfold drop in vaccine-induced antibody protection means an update is needed. That does not necessarily apply to this coronavirus.
“The problem is we don’t know what the cut point is for coronavirus,” said Dr. John Mascola, director of the Vaccine Research Center at the U.S. National Institute of Allergy and Infectious Diseases (NIAID), whose scientists helped develop Moderna’s vaccine.
Mascola said both studies testing the Moderna vaccine against the South African variant are roughly in the “same ballpark.” It could be that antibody protection is high enough from the vaccine that it will still be effective, he said.
NIAID scientists are analyzing data from Moderna’s late-stage trial to see what level of neutralizing antibodies is required for protection. They are comparing individuals who were vaccinated but got sick anyway to vaccinated people who remained healthy.
It could take two months to complete this work, Mascola said. They hope to produce a benchmark for the minimum level of vaccine-induced antibodies needed to protect against COVID-19.
A global surveillance network is also needed to identify troubling new variants as they emerge, similar to one used to track fast-mutating flu viruses. That could cost tens to hundreds of millions of dollars in the United States alone.
Richard Webby, a flu surveillance expert from St. Jude Children’s Research Hospital, said the United States could probably build a system to identify variants fairly quickly. Developing the capability to determine whether they evade current vaccines will take more time.
The United States is currently conducting genetic sequencing to look for changes in the virus in just 0.3% of positive coronavirus tests. That pales compared with 10% in the U.K., which was first to discover a major mutation in the virus that increases transmission by at least 50%. Experts said countries should sequence at least 5% of positive cases to detect significant changes in the virus.
Companies are waiting for the U.S. Food and Drug Administration to relay what testing will be needed for altered vaccines, said Phil Dormitzer, one of Pfizer’s top viral vaccine scientists. With influenza vaccines, companies can make changes without new trials. “But that’s after doing it for 50 years,” he said.
Peter Marks, who oversees the FDA’s vaccine approval process, has said small trials testing updated vaccines in around 400 participants may be needed at first. Even that could add months to the process.
Norman Baylor, chief executive of Biologics Consulting and a former FDA vaccines official, said the agency will lay out the regulatory road. But public health agencies like the U.S. Centers for Disease Control and Prevention and the World Health Organization would decide when vaccines should be updated, as with the flu.
Altering Pfizer’s vaccine would require “a very minor change,” Dormitzer said.
Like Moderna’s, it uses messenger RNA (mRNA) technology, which relies on synthetic genes that can be generated and manufactured in weeks.
He estimates the company could make a prototype version in a week or so, and take another two months to scale up and update their lab tests.
J&J, which is expected to release late-stage trial data on its vaccine within days, has laid the groundwork to address troubling virus changes, Chief Scientific Officer Paul Stoffels said. Its trial included sites in South Africa, which should give the company insight on that variant.
If a change is necessary, Stoffels said J&J likely would add a second strain into its existing vaccine.
“We are looking at this with a lot of attention,” he said.
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