William Buoni, MD - Wexner Medical Center

FDA Approves A New Covid-19 Booster, Targeting XBB.1.5

Recommended by the CDC for everyone over the age of 6 months, the latest Covid-19 booster ... [+] specifically targets XBB.1.5. (Photo by JOEL SAGET / AFP) (Photo by JOEL SAGET/AFP via Getty Images)

AFP via Getty Images

In the continuing effort to mitigate the effects of Covid-19, the U.S. Food and Drug Administration has approved for emergency use new Covid-19 vaccines. Additionally, the Centers for Disease Control and Prevention recommended these new boosters for everyone over the age of 6 months. These new formulations are better matched to currently circulating strains of the virus. And like the previously approved vaccines, they hopefully will decrease the rate of serious illness, hospitalization, and death among people infected with SARS-CoV-2, the virus that causes Covid-19.

The new vaccines, developed by Moderna and Pfizer-BioNTech, employ the same mRNA-based technology as the previously approved versions of their vaccines. However, the mRNA itself has been changed to reflect the changing virus. These latest vaccines contain mRNA that codes for the spike protein of the XBB.1.5 subvariant of omicron. Preliminary data show that this booster will trigger the production of antibodies that recognize this form of SARS-CoV-2. This booster also may provide improved protection against other circulating subvariants.

As we have seen throughout the pandemic, the virus evolves over time. The first Covid-19 vaccines, approved for use in December 2020, contained a segment of mRNA that coded for the spike protein of the original SARS-CoV-2 virus. Over time, though, viral variants that contained mutations in the gene coding for the spike protein arose. These mutations negatively affected the effectiveness of the original vaccines and prompted drug manufacturers to develop new formulations to better target new viral strains.

In response to the surge of Covid-19 cases associated with the omicron variant, for example, Moderna and Pfizer-BioNTech converted their vaccines from monovalent to bivalent. Approved for use in August 2022, these boosters contained two pieces of mRNA, one that coded for the spike protein of the original virus and one that coded for the spike protein of the BA.4 and BA.5 subvariants of omicron, which were dominant throughout the world at that point in time. By the end of 2022, however, the prevalence of these subvariants had declined and a new omicron subvariant, XBB.1.5, emerged. The prevalence of this subvariant quickly increased, prompting the development of the latest Covid-19 vaccine formulations.

But XBB.1.5 no longer is the dominant variant. In May 2023, XBB.1.5 accounted for about half of all Covid-19 infections in the U.S. By July, that number dropped to less than a quarter. Today, XBB.1.5 accounts for less than 5% of infections. During this time, the prevalence of another omicron subvariant, EG.5, has been increasing. This variant now accounts for roughly 25% of all infections.

And researchers are anxiously monitoring yet another subvariant, BA.2.86. Also referred to as Pirola, this subvariant was first detected in Denmark in July 2023. Since then, it has been detected in 15 countries, including the United States, according to the international virus tracking site GISAID. Thus far, the prevalence of this variant has remained low. But scientists remain concerned because of the large number of mutations that it possesses, especially within the spike protein gene. This constellation of changes, some researchers have worried, could allow this variant to evade existing vaccines and be more transmissible than its predecessors.

So, is the XBB.1.5 vaccine already obsolete? No. In a press release posted on September 6, 2023, Moderna announced that trial participants receiving their XBB.1.5-based vaccine produced neutralizing antibodies against EG.5 and BA.2.86. In other words, this new vaccine results in the production of antibodies that recognize the currently dominant subvariant and a potentially worrisome subvariant. Additionally, in a manuscript currently undergoing peer-review, researchers from Harvard University and Los Alamos National Laboratories report that, despite its numerous mutations, BA.2.86 may not be as capable of evading immunity as originally feared.

This new vaccine most certainly will provide better protection than the existing vaccines against the currently circulating Covid-19 strains. But what comes next? The virus will continue to evolve. That much is certain. For the foreseeable future, then, we probably can expect updated Covid-19 shots to be released periodically, in response to new variants. Perhaps, though, that will change. Researchers at various institutions, such as the Duke Human Vaccine Institute, are actively trying to develop a pan-coronavirus vaccine, a vaccine that can effectively inhibit multiple different coronaviruses. However, until that goal becomes a reality, we may be caught in a perpetual game of cat and mouse.

Pfizer, BioNTech File For FDA Approval Of COVID Booster Shot

Pfizer and BioNTech have formally asked for FDA approval of a third dose of their COVID-19 vaccine BNT162b2 in people aged over 16, as the US prepares to get its booster campaign underway.

The two companies have submitted data from a phase 1 trial in support of the booster dose to the US regulator, and will follow that with filings in Europe and elsewhere in the world in the coming weeks.

The move comes a few days after both the FDA and the Centres for Disease Control and Prevention (CDC) cleared emergency use of third doses of either the Pfizer/BioNTech or Moderna COVID-19 vaccines for people with "moderately to severely" weakened immune systems as well as solid organ transplant recipients.

Mixing of the two mRNA vaccines is permitted for the third shot if the original vaccine received by a person is not available, according to the agency.

The results of the safety and immunogenicity study show a favourable safety profile and "robust" immune responses after a third dose, said Pfizer and BioNTech in a statement.

"The data we've seen to date suggest a third dose of our vaccine elicits antibody levels that significantly exceed those seen after the two-dose primary schedule," said Pfizer chief executive Albert Bourla.

The study involved adults who had received two doses of BNT162b2 in the original phase 1 trials of the shot, and were then given a third dose between eight and nine months later.

According to the companies, the third dose stimulated significantly higher neutralising antibodies against the original 'wild-type' SARS-CoV-2 virus than after the two-dose regimen, as well as against the beta variant and the highly infectious delta strain.

"Vaccination is our most effective means of preventing COVID-19 infection – especially severe disease and hospitalisation – and its profound impact on protecting lives is indisputable," continued Bourla.

"Still, with the continuing threat of the delta variant and possible emergence of other variants in the future, we must remain vigilant against this highly contagious virus," he added.

Data from a larger phase 3 study of the third dose is also expected shortly and will be submitted to the FDA when available, said the drugmakers.

CureVac, GSK say new-generation jab is much improved

There was also encouraging news for CureVac and GlaxoSmithKline's COVID-19 vaccine programme, after the two partners said a new, improved version of their shot was much better at protecting against the virus in preclinical testing than their first effort.

Their first mRNA-based candidate was found to be just 47% effective in a phase 3 trial reported in June, below the threshold efficacy level for a vaccine laid out by the World Health Organisation (WHO) in the early stages of the pandemic and well short of rival shots.

The new CV2CoV version – which achieved "faster response onset, higher titres of antibodies, and stronger memory B and T cell activation" than its predecessor – is set to start human testing in the fourth quarter of this year.

It is designed to simultaneously tackle multiple variants of SARS-CoV-2, including beta, delta and lambda – which some studies suggest is even more transmissible than delta.

Feature image copyright BioNTech SE 2020, all rights reserved

FDA Schedules Adcomm For Pfizer's COVID Booster Filing

The FDA will hold an advisory committee meeting later this month to discuss Pfizer and BioNTech's filing for approval of a third booster dose of their COVID-19 vaccine Comirnaty in people aged 16 and over.

The adcomm is scheduled for 17 September and will consider the Pfizer/BioNTech filing as well as booster doses more generally. The news comes as Moderna has just announced the submission of initial data to the FDA for its own COVID-19 vaccine booster.

Whether expert meetings will be needed for other vaccines will depend on the data received by their manufacturers, and if it raises "unique questions that would benefit from the committee's input", said Peter Marks, director of the FDA's Center for Biologics Research and Evaluation (CBER).

The meeting has been announced shortly after two of the FDA's senior vaccine staff – Dr Marion Gruber and Dr Philip Krause – said they would be stepping down in the autumn, reportedly in protest at the US government's recent announcement of a booster campaign prior to an FDA ruling.

"The administration recently announced a plan to prepare for additional COVID-19 vaccine doses … and a key part of that plan is FDA completing an independent evaluation and determination of the safety and effectiveness of these additional vaccine doses," according to Marks, who will replace Gruber as head of the Office of Vaccines Research and Review on an interim basis while a successor is sought.

"A transparent, thorough and objective review of the data by the FDA is critical so that the medical community and the public continue to have confidence in the safety and effectiveness of COVID-19 vaccines," he added.

Pfizer and BioNTech said last week they had started a 'rolling' marketing application for a third dose of Comirnaty, after President Joe Biden announced plans to make boosters available this month to any adult American who has been fully vaccinated at least eight months ago.

The FDA has already issued an emergency use authorisation (EUA) for third doses of the Pfizer/BioNTech and Moderna jabs, but only for people with compromised immune systems. Several other countries, including the UK, have said they will start booster campaigns only in vulnerable populations.

The White House has insisted that any booster campaign will only start after the FDA review, but its decision to make a public announcement ahead of the regulator's verdict has been criticised as a move intended to raise political capital.

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