Summary
What are variant-adapted COVID-19 vaccines?
The COVID-19 vaccine developed by BioNTech and Pfizer is known as BNT162b2 (Comirnaty). BNT162b2 contains messenger RNA, or mRNA, from SARS-CoV-2. SARS-CoV-2 is the virus responsible for COVID-19. mRNA is a type of genetic material that contains the instructions that tell cells in the body how to make a protein. The mRNA in BNT162b2 tells the body to make one of the proteins from SARS-CoV-2 known as the spike protein.
This teaches the body’s defense system, known as the immune system, to recognize and respond to a SARS-CoV-2 infection.
The BNT162b2 vaccine contains mRNA from the first SARS-CoV-2 virus, which was detected in December 2019. Since this original vaccine was developed, the SARS-CoV-2 virus has evolved, resulting in the appearance of new versions of the virus, known as variants. Certain variants that might be more concerning for public health are labeled as either ‘variants of concern’ or ‘variants of interest’ by the World Health Organization (WHO). Variants have differences in their proteins compared with the original virus that can affect how well the original vaccine works against them. Therefore, BioNTech and Pfizer developed updated versions of the BNT162b2 vaccine that contain mRNA from certain variants. These new vaccines are called variant-adapted COVID-19 mRNA vaccines.
Another company, Moderna, has also developed their own variant-adapted versions of their COVID-19 mRNA vaccine, mRNA-1273 (SpikeVax).
Variant-adapted vaccines can contain parts of the variant mRNA either in addition to, or instead of, that from the original virus. Vaccines that contain mRNA from two different viruses are known as bivalent, whereas vaccines that contain mRNA from a single virus are called monovalent.
What is the purpose of this plain language summary?
The purpose of this plain language summary is to help you understand a recent publication about COVID-19 vaccines.
The authors of the original publication reviewed the existing literature about a type of COVID-19 vaccine called a variant- adapted vaccine.
Variant-adapted vaccines are developed to closely match new versions of the virus that causes COVID-19.
The original publication focused on variant-adapted COVID-19 vaccines developed by BioNTech and Pfizer.
Where can I find the original article on which this summary is based?
You can read the original article Pather S, Muik A, Rizzi R, Mensa F. Expert Rev Vaccines. 2023 Jan–Dec; 22(1):650-661. DOI: 10.1080/14760 584.2023.2232851. PMID: 37417000 here: https://doi.org/10.1080/14760584.2023.2232851. You can access the article for free.
Who sponsored this clinical study?
Why are variant-adapted vaccines needed?
The original BNT162b2 vaccine helps the immune system create antibodies designed to target the original SARS-CoV-2 virus. These antibodies recognize and bind to a protein found on the surface of the original SARS-CoV-2 virus. However, the shape of this protein in variants is different from that found in the original virus. This makes it more difficult for the original antibodies to recognize variants.
The following variant-adapted BNT162b2 vaccines have been approved for use around the world:
Bivalent original/Omicron BA.4–BA.5.
Monovalent XBB.1.5 (the BNT162b2 monovalent XBB.1.5 variant-adapted vaccine has been approved for use in the European Union [EU] by the European Medicines Agency [EMA], and in the United States by the United States Food and Drug Administration [FDA], since the publication of the original review article).
Variant-adapted vaccines allow the body to develop antibodies that more closely match the protein from a variant, making it better able to recognize and eliminate the variant virus (see figure below). Variant-adapted vaccines can provide improved protection against the specific variants included in the vaccines, as well as against other closely related viruses, when compared with the original vaccine.
How were the variants to include in the BNT162b2 vaccines chosen?
The first Omicron variant was detected in November 2021. The Omicron variant continued to evolve, leading to the appearance of several descendants, called sub-lineages, all with differences in their proteins.
Two of these sub-lineages, BA.4 and BA.5, caused a large increase in the number of infections. As they were not as well recognized as the original virus by antibodies generated by the original vaccine, a variant-adapted vaccine containing mRNA common to both BA.4 and BA.5 was developed to provide better protection against these sub-lineages.
The BA.4/BA.5 variant-adapted vaccine has been widely used to protect against Omicron sub-lineages. However, sub-lineages descended from a different variant, known as XBB, later emerged and have since become the most common sub-lineages around the world. XBB sub-lineages have several differences in their surface protein compared with other sub-lineages, such as BA.4 and BA.5, which could reduce the protection from existing vaccines.
Therefore, a variant-adapted BNT162b2 vaccine containing mRNA from an XBB descendent sub-lineage, XBB.1.5, has been developed. This vaccine has recently been approved around the world, including in Europe and the United States, and is being rolled out for use in the Northern Hemisphere autumn 2023/winter 2024 season.
What data are needed for the approval of variant-adapted vaccines?
The FDA and the EMA are regulatory agencies that decide whether new medicines and new vaccines
should be used in humans; this is called ‘approval’.
The FDA and EMA approved the original BNT162b2 vaccine based on data from large clinical trials that tested how well the vaccine protected against COVID-19. These trials showed that the vaccine was effective because vaccinated people were less likely to be infected by SARS-CoV-2 or have severe COVID-19 compared with unvaccinated people. More than 40,000 people took part in one of these trials, half of them receiving the vaccine, and they were monitored for at least 6 months after vaccination.
Data requirements for the approval of variant-adapted vaccines by other regulatory agencies may differ from those of the EMA and FDA.
As the efficacy and safety of the original BNT162b2 vaccine had already been proven, the FDA and EMA decided that large efficacy trials of the variant-adapted vaccines were not needed. Instead, these vaccines were approved based on data showing that the antibody response against the vaccine variant was higher than that of the original vaccine in animal models.
How will future variant-adapted vaccines be developed and approved?
In early 2023, the FDA, EMA, and WHO all held meetings to discuss whether the COVID-19 mRNA vaccines should be updated for the upcoming autumn/winter season. They recommended that variant-adapted vaccines containing mRNA from a sub-lineage descended from XBB, the most common circulating viruses at the time, should be developed.
The process used to determine the need for updates to COVID-19 vaccines is similar to that used for seasonal influenza (flu).
In future, it is expected that agencies, such as the FDA, EMA, and WHO, will meet at least once a year to discuss whether other updates to COVID-19 vaccines are needed. The decision is likely to be based on the differences between the existing vaccines and circulating variants at the time of the meetings.
Additional information
This is a plain language summary of an original article titled: Clinical development of variant-adapted BNT162b2 COVID-19 vaccines: the early Omicron era.
You can find the full article here https://www.tandfonline.com/doi/pdf/10.1080/14760584.2023.2232851. You can access the full article for free.
This summary was prepared in September 2023. The authors of the original article also prepared this summary. Medical writing and editorial support were provided by Rachel Wright, PhD, of Scion, London, UK, funded by BioNTech SE.
Funding disclosure
This manuscript was funded by BioNTech SE.
Declaration of interest
A Muik, S Pather, F Mensa, and R Rizzi are employees of BioNTech SE (Mainz, Germany). A Muik is an inventor on patents and patent applications related to RNA technology and COVID-19 vaccines. A Muik, S Pather, F Mensa, and R Rizzi have securities from BioNTech SE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or material discussed in the manuscript, apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
All authors substantially contributed to the article conception, writing, and review process, and approved the final version for submission.
Acknowledgments
Medical writing and editorial support were provided by Rachel Wright, PhD, of Scion, London, UK, funded by BioNTech SE.