FDA authorizes emergency use of bivalent booster shots that target omicron subvariant

On 31 August, the Food and Drug Administration (FDA) modified the emergency usage of bivalent formulations of  Pfizer-BioNTech and Moderna vaccines as a single booster dosage at least 2 months after the primary or booster immunization with any licensed monovalent coronavirus vaccine. The updated boosters consist of two messenger RNA (mRNA) components of coronavirus: (i) the original strain of coronavirus to facilitate a broadly protective immune response against coronavirus, and (ii) a strain from the BA.4 and BA.5 lineages of the Omicron variant to enhance defense against coronavirus disease elicited by highly contagious omicron variants.

The mRNA genetic material found in these vaccines commands cells to produce the unique "spike" protein of original strain and the omicron variant lineages  BA.5 and BA.4. The BA.4 and BA.5 spike proteins are similar. Bivalent (Moderna vaccine) is licensed for usage as a single booster dosage in individuals 18 years of age and above while Bivalent (Pfizer-BioNTech vaccine) is approved for usage as a single booster dosage in individuals 12 years of age and above. As per recent FDA sanctions, the monovalent mRNA coronavirus vaccines are not licensed as booster doses for people 12 years of age and above.

The revised approvals for each bivalent vaccine were in accordance with the totality of available evidence. The evidence encompassed: (i) extensive efficacy and safety data of monovalent vaccines, (ii) immunogenicity and safety information procured from research of bivalent vaccine that consisted of mRNA from the omicron variant BA.1 lineage that is comparable to each of the vaccines being licensed, and (iii) nonclinical data procured using a bivalent vaccine that comprised mRNA of original strain and mRNA in common between BA.4 and BA.5 lineages of the omicron variant. The bivalent vaccines are anticipated to offer an enhanced shield against omicron forms in accordance with the data supporting each of these approvals.

Who qualifies for a single booster dosage, and when?

• If it has been at least 2 months following the accomplishment of primary immunization or the latest booster dosage with any licensed monovalent vaccine, people 12 years of age and above are entitled for a single booster dosage of Pfizer-BioNTech vaccine, Bivalent.
• If it has been at least 2 months following the completion of primary immunization or the latest booster dosage with any licensed monovalent vaccine, people 18 years of age and above are entitled for a single booster dosage of Moderna vaccine, Bivalent.

Considerable caution has been taken by US-FDA to ascertain that these bivalent vaccines fulfil the stringent manufacturing quality, efficacy, and safety standards for emergency use authorization (EUA). The safety and immunogenicity data were examined from a study of a booster dosage of a bivalent coronavirus vaccination that included a component of original strain of coronavirus and  component of omicron lineage BA.1.

The FDA views these data as pertinent and in favor of vaccinations having a BA.4 or BA.5 lineage component of omicron variant. The agency's assessment was also influenced by information on the efficacy and safety of  existing mRNA coronavirus vaccinations, which have been given to millions of individuals, including during the omicron waves.

Data in Support of Moderna Vaccine Bivalent Approval

The FDA examined immune response data from about 600 volunteers who had previously received a 2-dose primary series and a single booster dosage of monovalent Moderna vaccine in order to assess the efficacy of a single booster dosage of the bivalent Moderna vaccine for adults 18 years of age and above. At least three months following the initial booster shot, volunteers were given a 2nd dose of either monovalent vaccine or investigational bivalent vaccine (omicron BA.1 and original). Following 28 days, volunteers who were given bivalent vaccine had stronger immune responses against BA.1 than volunteers who were only given the monovalent Moderna vaccine.

Moderna's investigational bivalent vaccine safety data from a trial exploring primary and booster immunization with monovalent vaccine, and postmarketing safety data with monovalent vaccine all favor safety of a single booster dose of bivalent vaccine for people 18 years of age and above. Since these vaccines are created using the same process, the safety data gathered with the monovalent vaccine and the bivalent vaccine are relevant to the Moderna vaccine, Bivalent.

About 800 volunteers (aged 18 and above) who were previously administered a 2-dose primary series and 1 booster dose of monovalent vaccine were a part of the clinical study that investigated safety of a booster dose of bivalent vaccine, and who were then administered a 2nd  booster dose with either monovalent vaccine or investigational bivalent vaccine, at least three months later.
 

The most frequently reported adverse effects among study volunteers who received bivalent vaccine were fever, discomfort, nausea/vomiting, swelling and redness at the injection site, fatigue, headache, muscle and joint pain, chills, and swelling of lymph nodes in the same arm of the injection.

Data in Support of Pfizer-BioNTech COVID-19 Vaccine Bivalent Approval
The FDA examined immune response data from 600 adults (older than 55 years) who were previously given a two-dosage primary series and one booster dosage with the monovalent vaccine in order to explore the efficacy of a single booster dosage of  bivalent vaccine for people 12 years of age and above. Following the first booster shot 4.7 and 13.1 months later, the volunteers got a second dose of either monovalent vaccination or the investigational bivalent vaccine (omicron BA.1 and original) from the same company.

Following 1 month, volunteers who were given the bivalent vaccine exhibited a better immune response against BA.1 than volunteers who were given the monovalent vaccine. In accordance with the safety data from a study that examined a booster dosage of investigational bivalent vaccine, safety data from trials that assessed primary and booster vaccination with the monovalent vaccine, and postmarketing safety data with the monovalent vaccine, assessment of safety of a single booster dosage of the bivalent vaccine was done.

The monovalent Pfizer-BioNTech vaccine and the bivalent Pfizer-BioNTech vaccine both have safety data that are relevant to each other because they were produced using the same manufacturing procedure. About 600 volunteers (age more than 55 years) who were earlier administered a 2-dose primary series, 1 booster dose of monovalent vaccine, and then given a 2nd  booster dose of either monovalent vaccine or investigational bivalent immunization 4.7 to 13.1 months later were included in the study that assessed safety of bivalent vaccine booster dose.

The most frequently noted side effects among trial volunteers who got the bivalent vaccine were fever, pain, redness and swelling at the injection site, exhaustion, joint pain, headache, muscle soreness, and chills. The FDA has also updated the EUAs for the Pfizer-BioNTech vaccine and the Moderna vaccine to eliminate the usage of monovalent versions of these vaccines for booster administration for people 12 years of age and above, and 18 years of age and above, respectively. As stated in the letters of permission, the usage of these monovalent vaccinations for the primary series administration to people six months of age and above is still permitted.

The Pfizer-BioNTech Vaccine is still licensed for usage in pediatrics (age 5 to 11 years) at least 5 months after finishing the initial series of single booster dose given.  Numerous lives are still being saved by SARS-CoV-2 vaccines, including boosters, which also avert the disease's most devastating consequences like death and hospitalization. It is strongly advised to get a booster dose of a bivalent COVID-19 vaccination in order to improve protection against presently circulating variants. For additional age groups, the US-FDA will assess upcoming information and submissions to expedite approvals of bivalent booster vaccines.