After deploying four COVID-19 shots in a little more than two years, the nation is absorbing a troubling realization: That’s a pace that’s impossible to sustain.
This past week, experts began charting a path to a future that is less perfect – but more practical.
It means building a vaccine that targets more than one strain of the virus. It would reduce severe disease and death, but not prevent every infection. If the design is changed, all vaccines will be updated. Manufacturers will likely offer the same vaccine formulation to everyone, rather than a mélange of different products for different people on different schedules.
And the goal is to have it ready by next fall when the risk of illness is likely to soar. That’s a very tight deadline.
Faced with the triple threats of fading immunity, an evolving virus and holiday gatherings, “we have to be prepared, from a standpoint of national security, making sure that we can protect our population with a vaccine in hand,” Dr. Peter Marks told an expert advisory FDA committee on Wednesday.
What will that look like?
“If we settle down to one shot per year that combines COVID and flu, I think that will be sustainable,” said UC San Francisco infectious disease expert Dr. Peter Chin-Hong.
“Nobody will want to get a vaccine every six months,” he said. “So we have to change the strategy.”
The creation and distribution of COVID-19 vaccines will go down in history as one of medicine’s greatest achievements. Only one year after cases were first documented, a shot was available. Fifteen months later, an impressive total of four doses were available for many people: a two-dose primary series and two boosters.
But, with each announced dose, interest fades. While 77% of the eligible U.S. population has gotten one shot, that rate dips to 65% who have gotten two shots and only 50% who have gotten three shots. The fourth dose is just beginning to be rolled out.
Vaccine protection is fading, too. After every shot, our immunity follows the same disappointing downward trajectory. Vaccines that are 91% effective in preventing hospitalization during the first two months fall to 78% after four months – and, over time, keep declining.
This means that people who got their one shot back in early 2021 are increasingly vulnerable.
Funding also will fade. Today’s federal funding free-for-all strategy won’t continue indefinitely, predict experts. Costs will be shifted to private insurers. That puts pressure on efficiency and effectiveness.
Yet the virus is here to stay. And it will keep changing. The virus has mutated two to 10 times faster than the flu, depending on the strain, reported virologist Trevor Bedford of the Fred Hutchinson Cancer Research Center in Seattle. He said it will continue mutating a little or a lot – either is possible.
Initially, experts hoped that a three-dose regimen would offer long-term protection. That strategy works for measles, mumps, rubella, hepatitis B, HPV and other viruses.
But COVID is different because it changes more, said Chin-Hong. That creates special challenges for vaccination planning.
This means things must move fast. The FDA hopes to decide on the composition of a future vaccine in May or June. While some clinical trials of potential products are already underway, vaccine manufacturers need several months to produce enough doses of a reconfigured vaccine, according to Robert Johnson, director of an infectious disease division within the Department of Health and Human Services.
The panel agreed on these points:
• The promise of a new “bivalent” or “multivalent” vaccine.
There’s a diminishing return by repeatedly giving the same “monovalent” vaccine, which targets the original strain, especially as new variants emerge. It also seems unlikely that an omicron-specific booster is the best idea. The virus changes so frequently that it could quickly be out of date.
A better approach may be to design something that targets two or more strains of the virus, called a “bivalent” or “multivalent” vaccine. Such vaccines are already in the works at Moderna and Novovax.
“A multivalent vaccine is going to be important in hopefully prolonging the duration of protection,” said Dr. Mark Sawyer, professor of clinical pediatrics at UC San Diego.
• Therapeutics must play a growing role.
Rather than constantly adding vaccines, we should seek the help of antiviral drugs, monoclonal antibodies and other future therapies to treat infections to keep people out of hospitals.
With 80% protection against hospitalization in older and sicker adults, “I think we may have to accept that level of protection and then use other alternative ways to protect individuals with therapeutics and other measures,” said Amanda Cohn of the U.S. Centers for Disease Control and Prevention.
• Take a more unified approach to manufacturing.
Vaccine makers should target the same strains, using similar doses, panelists said. It will prove impossible to keep track of multiple vaccines with different compositions.
The CDC must take the lead in deciding when the vaccines are no longer effective against severe illness, said Dr. Paul Offit, professor of pediatrics at The Children’s Hospital of Philadelphia. “At some level, the companies kind of dictate the conversation here,” he said.
If a new vaccine is needed to respond to a scary variant, it won’t just be a booster. The whole two-dose “primary series” would be replaced.
Better data and new designs are needed.
Because we’re in a rush, we’re relying on what the data tells us about the immune response in blood. But we also need to get better at interpreting what these lab studies mean for protection out in the real world, said Dr. Hayley Ganz, professor of pediatrics at Stanford University Medical Center. Antibody counts are important, she said. But so are other parts of the immune system, as well as clinical outcomes.
Finally, we need to know what future products await us in the research pipeline, even if they are not yet FDA authorized.
“The current mRNA vaccines are great. They can be turned around quickly,” said infectious disease expert Dr. Ofer Levy of Boston Children’s Hospital. “But it may be that other platforms emerge that give broader protection. So as we move forward, we don’t want to bake in a system that excludes other types of vaccines.”