The original Moderna vaccine contains 100 mcg of mRNA in each shot.
The FDA submission is supported by data that shows robust antibody responses for the booster vaccine against the Delta variant, said Stéphane Bancel, CEO, Moderna.
"We remain committed to staying ahead of the virus and following the evolving epidemiology of SARS-CoV-2. We will continue to generate data and transparently share to support governments and regulators as they make evidence-based decisions regarding future vaccination strategies.”
'Waning antibody levels'
The Phase 2 study of mRNA-1273 was amended to offer a booster dose of mRNA-1273 at the 50-microgram dose level to interested participants six months following their second dose, said the company.
The vaccine was still about 93% effective six months after the second dose, but Moderna saw that antibody levels had waned significantly by that timeline.
It said that some 344 participants of its original Phase 2 trial were given a third vaccine dose that generated a better immune response than what was seen after the second dose in the company’s Phase 3 study. “A booster dose of mRNA-1273 at the 50 µg dose level boosted neutralizing titers significantly above the Phase 3 benchmark. After a third dose, a similar level of neutralizing titers was achieved across age groups, notably in older adults (ages 65 and above).”
The US biotech said the safety profile of the third dose was similar to that of the second dose. The data are still to be submitted to a peer-reviewed publication, said Moderna.
Additional analysis showed that a booster dose of mRNA-1273 at the 50 mcg dose level induced robust antibody responses and significantly increased geometric mean titers (GMT) for all variants of concern including Beta (B.1.351) by 32- fold, Gamma (P.1) by 43.6-fold and Delta (B.1.617.2) by 42.3-fold, confirmed the company.
Moderna said it also expects to submit data on a booster vaccine to the European Medicines Agency (EMA) and other regulatory authorities around the world in the coming days.
In a business update early August, the company outlined its rationale for developing a booster shot: "We believe that increased force of infection resulting from Delta, non-pharmaceutical intervention (NPI) fatigue, and seasonal effects (moving indoors) will lead to an increase of breakthrough infections in vaccinated individuals. While we see durable Phase 3 efficacy through six months, we expect neutralizing titers will continue to wane and eventually impact vaccine efficacy. Given this intersection, we believe a [third dose, a booster] will likely be necessary prior to the winter season."
The FDA is currently evaluating a COVID-19 booster shot application by Pfizer-BioNTech.
ECDC: No urgent need for the administration of booster doses
Interestingly, in a document published today, the European Center for Disease Prevention and Control (ECDC), said the available evidence at this time regarding ‘real world’ vaccine effectiveness and the duration of protection shows that all vaccines authorized in the EU/EEA are currently highly protective against COVID-19-related hospitalization, severe disease and death.
Such evidence thus suggests, said the agency, that there is no urgent need for the administration of booster doses of vaccines to fully vaccinated individuals in the general population.
“The option of administering an additional vaccine dose to people who may experience a limited response to the primary series of COVID-19 vaccination, such as some categories of immunocompromised individuals (e.g. solid organ transplant recipients), should already be considered now. This is to be seen as an extension of the primary vaccination series for these specific groups, and not as a booster.
“Consideration could also be given to providing an additional dose as a precautionary measure to older frail individuals, in particular those living in closed settings (e.g. residents of long-term care facilities).”
More solid data are needed to inform future policies on booster doses, argued the ECDC.
“Knowledge gaps are particularly related to the appropriate correlate of protection to consider for the different population groups and the time from primary vaccination series until a booster dose should be given, and duration of immunity according to e.g. different age and risk groups, vaccine product, dosing interval, variant of concern (VOC), and homologous/heterologous schedule. Prospective vaccine effectiveness studies, as well as surveillance of breakthrough infections in the general population and in specific groups, are needed to answer these questions.”
The agency also stressed that, in the context of many countries outside of the EU/EEA still struggling to receive and administer enough vaccine doses to their populations, special consideration should be given to the current global shortage of COVID-19 vaccines, which could be further worsened by the administration of booster COVID-19 vaccine doses for the general population in EU/EEA countries.
