The following essay is reprinted with permission from The Conversation, an online publication on the latest research.
On August 31, 2022, the Food and Drug Administration authorized the use of updated COVID-19 booster shots specifically tailored to combat the two most recent and infectious omicron subvariants, BA.4 and BA.5. After FDA approval for emergency use, the Centers for Disease Control and Prevention is expected to approve the injections so they can be administered within days.
The new booster shots – one from Moderna and another from Pfizer-BioNTech – come as more than 450 people are still dying from COVID-19 in the US every day
As of August 31, 2022, only 48.5% of those eligible for a booster in the US have received their first booster shot, and just under 34% of those eligible have received their second. These low numbers may be partly affected by people waiting for the newer versions of the vaccines to provide better protection. But booster shots have proven to be an essential layer of protection against COVID-19.
Prakash Nagarkatti and Mitzi Nagarkatti are immunologists who study infectious diseases and investigate how vaccines activate different aspects of the immune system to fight infection. They weigh in on how the updated booster shots train the immune system and how protective they can be against COVID-19.
1. What’s different about the updated booster shots?
The newly authorized shots are the first updates to the original COVID-19 vaccines introduced in late 2020. They use the same mRNA technology as the original vaccines. The main difference between the original COVID-19 shots and the new “bivalent” version is that the latter consists of a mixture of mRNA encoding the spike proteins of both the original SARS-CoV-2 virus and the more recent omicron subvariants, BA.4 and BA.5.
As of the end of August 2022, the BA.4 and BA.5 omicron subvariants are dominant worldwide. In the US, currently 89% of COVID-19 infections are caused by BA.5 and 11% by BA.4.
The inability of the original vaccine strains to prevent reinfection and to induce long-term protective immunity led to the need for reformulated vaccines.
2. How does a bivalent vaccine trigger an immune response?
In actual COVID-19 infection, the SARS-CoV-2 virus uses its excellent spike protein to attach to and enter human cells. The spike protein activates the production of so-called neutralizing antibodies, which bind to the spike protein and prevent the virus from entering other cells.
But when the virus mutates, as we know, the antibodies that were previously produced in response to the virus can no longer effectively bind to the newly mutated spike protein. In this regard, the SARS-CoV-2 virus behaves like a chameleon — a master of disguise — changing its body configuration and escaping recognition by the immune system.
The persistent viral mutations are why antibodies produced in response to the original vaccine strains have become less effective over time at fighting off infection from new variants.
The concept of bivalent vaccines to protect against two different virus strains is not new. For example, Cervarix is an FDA-approved bivalent vaccine that protects against two different types of human papillomaviruses that cause cancer.
3. How protective are the new injections against infection?
There are no human studies yet on the efficacy of the new bivalent vaccine in preventing reinfection and providing long-term immune protection.
However, in human clinical trials and laboratory studies, both Pfizer-BioNTech and Moderna found that their first version of the bivalent vaccine, which targeted the original SARS-CoV-2 virus and an earlier omicron strain, BA.1, had a strong immune response and longer protection against both the original strain and the BA.1 variant. In addition, the companies reported that the same early combination generated a significant antibody response against the newest omicron subvariants, BA.4 and BA.5, although this antibody response was lower than that against subvariant BA.1.
Based on those results, the FDA rejected the BA.1 bivalent boosters in the spring of 2022 because the agency felt the boosters would not provide adequate protection against the newest strains, BA.4 and BA.5, which were then rapidly spreading. spread throughout the country. the US and the world. So the FDA asked Pfizer-BioNTech and Moderna to develop bivalent vaccines that specifically target BA.4 and BA.5, rather than BA.1.
Because clinical trials are time-consuming, the FDA was willing to consider animal studies and other lab findings, such as the ability of antibodies to neutralize the virus, when deciding whether to approve the bivalent boosters.
This decision has sparked controversy over whether it is appropriate for the FDA to approve a booster without direct human data to back it up. However, the FDA has stated that millions of people have safely received the mRNA vaccines — which were originally tested on humans — and that the changes in the mRNA sequences in the vaccines do not affect the vaccine’s safety. So it concluded that the bivalent vaccines are safe and there is no need to wait for human clinical trials.
It is also noteworthy that flu vaccines are introduced every year based on the prediction of the strain likely to be dominant, and such formulations are not undergoing new clinical trials.
Based on the available evidence from the previous COVID-19 vaccines, we believe it is highly likely that the new boosters will continue to provide strong protection against severe COVID-19 leading to hospitalization and death. But whether they will protect against reinfection and breakthrough infections remains to be seen.
4. Will it just be a booster shot?
The bivalent vaccines can only be used as a booster shot at least two months after the completion of the primary series — or the first required shots — or after a previous booster shot. The Moderna bivalent vaccine is approved for use in individuals 18 years of age, while the Pfizer bivalent vaccine is approved for use in individuals 12 years of age and older.
Because of the superiority of the bivalent vaccines, the FDA has also revoked the use authorization for the original monovalent Moderna and Pfizer COVID-19 vaccines for booster purposes in individuals 18 years of age and older and 12 years of age and older, respectively.
The new bivalent vaccines contain a lower dose of mRNA and as such are intended to be used only as boosters and not in people who have never received a COVID-19 vaccination.
5. Do the new shots protect against future variants?
How well the bivalent vaccines will perform in the face of new variants that may emerge will depend on the nature of future spike protein mutations.
If it is a small mutation or series of mutations compared to the original strain or to the ommicron variants BA.4 and BA.5, the new injections will provide good protection. However, if a hypothetical new strain had very unique mutations in its spike protein, it’s likely that it could evade immune protection again.
On the other hand, the successful development of the updated vaccines demonstrates that the mRNA vaccine technology is agile and innovative enough that – within a few months of the emergence of a new variant – it is now likely to be possible to develop and distribute new vaccines. those are tailored to combat an emerging variant.
This article was originally published on The Conversation. Read the original article.