World Health Leaders Discuss Long-Term Strategy for COVID-19 Vaccines and Boosters

Health officials around the world are grappling with developing a long-term strategy for COVID-19 vaccines and boosters as the COVID-19 pandemic evolves.

“It wouldn’t surprise any of us, in fact we rather anticipate that we will have to get a periodic booster. What the interval is we don’t know,” William Schaffner, MD, medical director of the National Foundation for Infectious Diseases (NFID) told Contagion.

What those vaccines might look like also is yet to be determined.

The World Health Organization and the European Medicines Agency recently have released public statements questioning the sustainability of repeated boosters of current vaccines. And current vaccines, which proved to be highly effective during earlier phases of the pandemic, have lost some of their punch against infection and transmission of the Omicron variant.

Preliminary data from an Israeli study led by Sheba Medical Center found that a fourth dose of Pfizer and Moderna COVID-19 vaccines raised antibody levels but was only partially effective against the Omicron variant.

Throughout the world, 139 COVID-19 vaccines are currently in clinical development and 194 are in pre-clinical development, according to the World Health Organization.

Some investigators are working on combining COVID-19 vaccines with influenza vaccines, Schaffner said. Following the influenza vaccine model, these shots would be updated twice a year—once in the southern hemisphere and once in the northern hemisphere.

“Now, we’d have to work very hard at that because we don’t cover nearly as many people with annual flu vaccines as we would like,” Schaffner said. “So, we would be constantly on an annual basis trying to implore, persuade, cajole people into getting their annual flu/COVID vaccines going forward.”

Another possible challenge would be the emergence of a new highly contagious variant that causes more severe disease and could evade immune protection, requiring a new vaccine to be formulated to meet the challenge.

“Let’s not get too definitive about this,” Schaffner said. “Let’s stay flexible and see what happens because we’re still in a responsive mode. We’re still chasing COVID, and we’ll be doing that for a while until we see a pattern really settle in.”

Chasing virus variants is challenging. Vaccine developers are working on vaccines to target the Omicron variant. But, by the time a variant-specific vaccine could be widely distributed, it could be too late, as signs are emerging that the Omicron surge may already be slowing in some areas.

A more universal COVID-19 vaccine, such as the Spike Ferritin Nanoparticle (SpFN) COVID-19 vaccine being developed by investigators at the Walter Reed Army Institute of Research (WRAIR), may provide protection against a wide variety of COVID-19 strains.

“That’s been the holy grail on the influenza side for the last 20 years, and we’re not there yet,” Schaffner said. “We’ll see how the science works out. We’ll just have to take it one step at a time.”

Presently, the US Centers for Disease Control and Prevention recommends boosters of current vaccines five months after the primary vaccination series for everyone aged 12 and older. Some immunocompromised people aged 5 and older are eligible to receive a third primary dose of the vaccine 28 days after their second dose. Some countries, including Israel, have approved fourth doses.

That strategy might work for now, but global health officials are searching for more sustainable alternatives, with an eye toward a shift in COVID-19 from a pandemic to endemic status.

WORLD HEALTH ORGANIZATION

In a statement released on Jan. 11, WHO said, “a vaccination strategy based on repeated booster doses of the original vaccine composition is unlikely to be appropriate or sustainable.” Among the considerations to weigh are “near- and medium-term supply of the available vaccines, the need for equity in access to vaccines across countries to achieve global public health goals, programmatic considerations including vaccine demand, and evolution of the virus.”

While urging vaccine developers to collect and share more data on effectiveness of vaccines against new variants, WHO also noted the importance of other mitigation strategies.

“Vaccines alone do not prevent the spread of COVID,” WHO said in a statement to Contagion. “Everyone, at a government and individual level, must continue a science-based, comprehensive approach in public health and social measures to stop transmission and prevent the further mutation of the virus.”

WHO’s Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC), is encouraging vaccine developers to share data on whether strain composition of COVID-19 vaccines should be changed.

“The current vaccines may not fully prevent you from getting infected or passing on the infection, but they will likely prevent you from getting severely ill, needing to go to the hospital, and dying,” WHO told Contagion® “As vaccines continue to remain effective against severe disease and death, those who are offered the vaccine should certainly take it. Increasing vaccine coverage will also help mitigate the emergence and impact of new VOCs.”

The group recognizes a need for broader access to vaccines and for development of vaccines that have a high impact on preventing infection and transmission. They encourage vaccine developers to gather and share data on the breadth and magnitude of immune response for monovalent and multivalent vaccines against variants of concern.

“The group also emphasized that while some countries recommend boosters, the immediate priority for the world is accelerating access to primary vaccination, particularly for groups at greater risk of developing severe disease,” WHO told Contagion. “The overwhelming majority of people admitted to hospitals around the world are unvaccinated.”

Aggressive booster programs could increase global inequity to vaccines and strain supplies. WHO will evaluate input from various stakeholders to determine guidance on the appropriate number of vaccine doses.

“Careful consideration of the evidence supporting what should be defined as ‘fully vaccinated’ for each vaccine product and type of vaccine recipient is required before WHO can issue further guidance,” WHO told Contagion.

Among considerations are whether people who have received two doses of a vaccine can travel to countries that define primary vaccination as three doses.

WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) is set to meet Jan. 19 to propose recommendations for the use of COVID-19 vaccines.

EUROPEAN MEDICINES AGENCY

The European Medicines Agency also has cautioned against repeated booster doses of current vaccines over the long term.

Marco Cavaleri, head of biological health threats and vaccines strategy with the European Medicines Agency said during a Jan. 11 news briefing that it is increasingly clear that booster doses are necessary to strengthen the immune response and extend vaccine protection during the Omicron wave. But he said repeating boosters every 3 or 4 months could be detrimental.

Cavaleri reiterated that position during a Jan. 18 press briefing, adding that members of the International Coalition of Medicines Regulatory Authority (ICMRA) agreed during a recent workshop that the administration of multiple booster doses at short intervals would not be sustainable in the longer term.

“One of the reasons is that running large vaccination campaigns repeated times per year is challenging from the operational perspective and is expected to lead to social fatigue amongst citizens,” he said.

Also, he said, the immune system needs time to mount a response to vaccines, and repeating doses too close together could make vaccination less efficient over time.

“If revaccinations would turn out to be needed, at least in some risk groups, it could be desirable to synchronize the vaccinations with the arrival of the cold season, similarly to what is done for influenza, so to increase the antibody response right at the time when it’s mostly needed,” Cavaleri said.

In the short term, administering a fourth dose of current vaccines in response to the Omicron wave is a topic of discussion.

“At the moment there is no evidence from available clinical or real-life data on the need and value of a fourth dose in the general population and with the current vaccines,” Cavaleri said. “However, once new evidence will accumulate, we will review the data as always to determine if any recommendation in this respect would be warranted.

“In people with severely weakened immune systems, however, even though no data are yet available, it would be reasonable for public health authorities to consider the administration of a fourth dose already now.”

Cavaleri also said more data is needed to determine whether an adaptive vaccine with a different composition is warranted to address the Omicron wave and other variants of concern. Regulators are encouraging vaccine developers to examine the feasibility of bivalent or multivalent vaccines along with monovalent vaccines to determine the best option.

“This is an ongoing global discussion that sits at the crossroads of science, public policy and public health and one that will require coordination among numerous stakeholders,” Cavaleri said. “The decision to update the vaccines warrants collaboration among public health decision-makers at all levels.”

Public acceptance of vaccines is an ongoing challenge for public health officials, who continue to urge people to adhere to current guidance and get vaccinated and boosted as soon as possible.

“I think what is unfortunately very sad to see throughout these months is that the intensive care units and the hospitals are filled with people that got infected and were not vaccinated,” Cavaleri said on Jan. 11. “The vast majority of those who get severe COVID-19 and eventually die of COVID-19 are people who have not received the vaccines and could do so. This is really disheartening. We would really encourage everybody to reconsider. It’s never too late. It’s important that everybody take advantage of the availability of vaccines and get vaccinated as soon as possible.”