CHICAGO, Jan. 28 (Reuters) – After developing and rolling out COVID-19 vaccines in record time, drug manufacturers are already facing variants of the rapidly evolving coronavirus that may render them ineffective, a challenge that will require months of research and a huge 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 to date. That’s just part of the work it takes to stay ahead of the virus, nearly a dozen experts told Reuters.
A global surveillance network must be built to assess emerging variants. Scientists need to determine the level of antibodies required to protect people against COVID-19 and determine when to change vaccines. And regulators must specify what it takes to demonstrate that updated vaccines are still safe and effective.
“At present, there is no evidence that these variants have changed the comparison in terms of vaccine protection,” said Dr. Michael Osterholm, an infectious disease expert at the University of Minnesota. “But we have to be prepared for that.”
Johnson & Johnson told Reuters that the affected variant first identified in South Africa has caught his eye and will adjust its vaccine as needed. Pfizer said it could produce a new vaccine relatively quickly, but a top vaccine manager said manufacturing it poses additional challenges.
The urgency of this effort is clear.
Moderna said on Monday that laboratory studies have shown that antibodies made in response to the vaccine were six times less effective at neutralizing a lab-made version of a South African variant than previous versions of the virus.
A study released Wednesday prior to peer review found that the South African variant reduced neutralizing antibodies 8.6 times for the Moderna vaccine and 6.5 times for the Pfizer / BioNTech injection, although a separate Pfizer-backed study released Wednesday suggests the vaccine may be more hardy. Moderna said this week that it is starting to work on a possible booster shot.
CAN TAKE MONTHS
How far protection can drop before a COVID-19 vaccine needs to be changed is not yet known. With influenza, an eight-fold decrease in vaccine-induced antibody protection means time to update. That does not necessarily apply to this corona virus.
“The problem is we don’t know what the intersection point is for the coronavirus,” says Dr. John Mascola, director of the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center, whose scientists helped develop Moderna’s vaccine.
Mascola said both studies testing the Moderna vaccine against the South African variety go in roughly the same direction. It may be that the antibody protection provided by the vaccine is high enough to still be effective, he said.
NIAID scientists analyze data from Moderna’s late-phase study to see what level of neutralizing antibodies is needed for protection. They compare individuals who have been vaccinated but become ill with vaccinated people who have remained healthy.
It can take up to two months to complete this work, Mascola said. They hope to produce a benchmark for the minimal 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 detect fast-mutating flu viruses. That could cost tens to hundreds of millions of dollars in the United States alone.
Richard Webby, an influenza surveillance expert at St. Jude Children’s Research Hospital, said the United States could likely build a system to identify variants fairly quickly. Developing the ability to determine whether they are avoiding current vaccines will take more time.
The United States is currently performing genetic sequencing to look for changes in the virus in just 0.3% of positive coronavirus tests. That pales in comparison to 10% in the UK, which was the first to discover a major mutation in the virus that increases transmission by at least 50%. Experts said countries need to 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 report what tests are needed for modified vaccines, said Phil Dormitzer, one of Pfizer’s top viral vaccine scientists. Flu vaccines allow companies to make changes without new trials. “But that’s after fifty years of doing,” he said.
Peter Marks, who oversees the FDA’s vaccine approval process, has said that small tests may be needed in the beginning to test updated vaccines in about 400 participants. Even that can add months to the process.
Norman Baylor, chief executive of Biologics Consulting and a former FDA vaccines official, said the agency will chart the regulatory path. But public health agencies like the U.S. Centers for Disease Control and Prevention and the World Health Organization would decide when to update vaccines, such as in the case of flu.
Changing 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 produced in weeks.
He estimates the company could be making a prototype version in a week or so, and it will take two more months to scale up and update their lab tests.
J&J, which is expected to release data on its late-stage vaccine within days, has laid the groundwork to address troubling virus changes, Chief Scientific Officer Paul Stoffels told Reuters. The trial included locations in South Africa, which should give the company insight into that variant.
If a change is needed, Stoffels said J&J would likely add a second strain to its existing vaccine.
“We look at this with a lot of attention,” he said.
Reporting by Julie Steenhuysen in Chicago and Michael Erman in New York; Edited by Caroline Humer and Bill Berkrot