FDA suggests future of COVID-19 vaccination may look like a more frequent flu shot

The U.S. Food and Drug Administration says that the currently approved COVID-19 vaccines may need to update their formulas to remain effective against the most recent strains of coronavirus, suggesting that the future of COVID-19 vaccination may be similar to the flu shot.

On Wednesday, the FDA's vaccine advisory committee will meet to discuss "the future course of the pandemic," including what the "optimal strain composition for COVID-19 vaccines" will be and the best schedule for vaccine booster doses among the general population and sub-groups that may be more vulnerable to the virus, according to a briefing document published ahead of the meeting.

The document acknowledges that the current authorized or approved COVID-19 vaccines in the U.S. "are based on the original Wuhan strain" and that "currently circulating SARS-CoV-2 variants harbor mutations" to the virus' spike protein, the feature of a virus that enables it to invade human cells. Studies have shown that these mutations, variants like the B.A. 2 Omicron strain, have reduced the effectiveness of the vaccines currently in use and also that the vaccines have waning efficacy over time, the FDA said.

"New variants are often more infectious, transmissible, and antigenically distinct from earlier virus strains due to accumulated mutations in the [spike] protein that also render them less susceptible to neutralization by antibodies elicited by current COVID-19 vaccines or prior infection by earlier strains of virus," the document states.

During Wednesday's meeting, the FDA's expert advisers will discuss how the agency can develop a transparent process to make recommendations for changing the current composition of the vaccines, if that becomes necessary.

"Although a complete understanding of how emerging SARS-CoV-2 variants impact the effectiveness of current COVID-19 vaccines is lacking, the accumulating data suggest that the composition of vaccines may need to be updated at some point to ensure the high level of efficacy demonstrated in the early vaccine clinical trials," the FDA said.

"An orderly, logical, and transparent process should be delineated for making recommendations for possible changes in COVID-19 vaccine composition and will require the cooperation and collaboration of vaccine manufacturers, vaccine regulators, and global public health laboratories."

When the vaccines were first approved, they showed a 90% efficacy against the original Wuhan strain of coronavirus, according to the U.S. Centers for Disease Control and Prevention. But after the emergence of new variants, including the Delta, Omicron, and B.A. 2 Omicron sub-variants, vaccine efficacy was shown to decline over time.

Citing data from the U.K. Health Security Agency, CNBC News reports that the effectiveness of Pfizer's or Moderna's two-dose vaccines against mild illness caused by the Omicron variant dropped from 70% to just 10% in 25 weeks after the second shot. A booster dose brought protection back up to 75% for about four weeks, but then it fell to between 25% and 40% after 15 weeks.

CDC data shows a corresponding waning efficacy for the vaccines' protection against hospitalization from Omicron. While two vaccine doses initially reduced the incidence of hospitalization by 71%, in five months the effectiveness fell to 54%. A booster dose brought protection back up to 91%, but then it fell again to 78% after four months.

Importantly, the vaccines remain effective at preventing most severe or life-threatening COVID-19 infections and hospitalizations.

For those who are unvaccinated but have previously contracted COVID-19, natural immunity gained from that infection appears to be of longer duration than vaccine-induced immunity, according to an Israeli study. Other studies have shown that the risk of COVID-19 reinfection is low in those with natural immunity and also that vaccination after prior infection can reduce the risk even further.

The Biden administration continues to recommend that all Americans eligible to get vaccinated and receive booster doses do so, especially people with pre-existing health conditions that make them more vulnerable to the virus.

Given uncertainty about how the coronavirus will mutate in the future, the FDA says that clinical trial data to determine safety and efficacy will be necessary before any changes to the current composition of the vaccines are approved. Pfizer and Moderna are currently conducting clinical trials for a new vaccine formula based on the Omicron variant and the BA.2 sub-variant, which has caused a surge of breakthrough infections associated with mild illness in both Europe and the United States.

The FDA briefing document also discusses the timing for additional COVID-19 vaccine booster shots and which groups of people will be eligible for those shots.

The document suggests that in the future, COVID-19 vaccination will be similar to the yearly flu shot, where scientists identify the most likely variant of the virus to circulate seasonally and base that year's vaccine dose on that variant.

"While influenza and coronaviruses are different viruses and will undoubtedly evolve and behave differently in the human population, the process for updating influenza vaccine composition may provide some useful guidelines and considerations for possible updating of COVID-19 vaccine composition," the FDA states.

However, there are important differences between the influenza virus and COVID-19. While the flu has a predictable pattern of emerging each winter, the FDA says "a predictable pattern for a SARS-CoV-2 surge of infections has yet to emerge; for example, Delta and Omicron virus surges in the U.S. were separated by only about 5 months." It is also unclear whether COVID-19 vaccine manufacturers can update the compositions of their vaccines and mass produce them quickly enough to keep up with the evolving virus. Additionally, the flu shot does not need to be tested for safety and efficacy each year, but the COVID-19 vaccines would need testing before each new composition.

These considerations, as well as the role of the World Health Organization in recommending each new COVID-19 vaccine composition, as it does for the flu shot, will be discussed Wednesday.

Last week, U.S. officials authorized a second COVID-19 booster shot (fourth dose) for all Americans over the age of 50, after data showed waning vaccine immunity against the Omicron variants. The FDA said this shot could be administered as early as four months after the first booster dose.

Dr. Peter Marks, an official who leads the FDA office responsible for vaccine safety, said last week that the U.S. may need to offer fourth booster shots for people under 50 in the fall and fifth boosters for those who have already received their fourth dose. He told reporters on a conference call that the extra doses may be necessary as vaccine-induced immunity continues to wane and new virus variants become seasonal.

“It would not be surprising if there is a potential need for people to get an additional booster in the fall along with a more general booster campaign if that takes place,” Marks said. “It may be that a decision is made that rather than the vaccines we currently have, which are called vaccines against the prototype virus, that we will move to a vaccine that is either against one of the variants or something else.”

According to federal data, roughly 45% of Americans who have completed their primary COVID-19 vaccination schedules have also received a booster dose.