Prakash Nagarkatti
and
Mitzi Nagarkatti
are immunologists who study infectious disorders and how vaccines trigger 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 might be against COVID-19.
1. What is different about the updated booster shots?
The newly authorized shots are the first updates to the original COVID-19 vaccines that were introduced in late 2020. They use the same
mRNA technology as the original vaccines
. The key difference between the original COVID-19 shots and the new “bivalent” version is that the latter consists of a mixture of mRNA that encodes the
spike proteins
of both the original SARS-CoV-2 virus and the more
recent omicron subvariants, BA.4 and BA.5
.
As of late August 2022, the BA.4 and BA.5 omicron subvariants are dominant worldwide.
In the U.S., currently
89% of COVID-19 infections are caused by BA.5 and 11% are caused by BA.4.
The booster shots target the BA.4 and BA.5 subvariants of the omicron variant, as well as the original version of SARS-CoV-2, the virus that causes COVID-19.
2. How does a bivalent vaccine trigger an immune response?
In an actual COVID-19 infection, the SARS-CoV-2 virus uses its protruding
spike protein to latch onto human cells
and gain entry into cells. The spike protein triggers the production of so-called
neutralizing antibodies
, which bind to the spike protein and prevent the virus from invading other cells.
But
when the virus mutates
, as we know that it does, the antibodies that were previously produced in response to the virus can no longer effectively bind to the newly mutated spike protein. In this respect, the SARS-CoV-2 virus acts like a chameleon – a master of disguise – by changing its body configuration and escaping recognition by the immune system.
The ongoing viral mutations are why antibodies produced in response to the original vaccine strains have over time become less effective at fending off infections by new variants.
The concept of bivalent vaccines aimed at protecting against two different strains of a virus is not new. For instance,
Cervarix is an FDA-approved bivalent vaccine
that provides protection against two different types of human papillomaviruses that cause cancer.
3. How protective will the new shots be against infection?
There are as of yet no human studies on the efficacy of the new bivalent vaccine at preventing reinfections and providing long-term immune protection.
However, in human clinical trials and laboratory studies,
both Pfizer-BioNTech and Moderna found
that their initial version of the bivalent vaccine, which was directed against the original SARS-CoV-2 virus and an earlier omicron strain, BA.1, induced 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, though this antibody response was lower than that seen against subvariant BA.1.
Based on those results, in spring 2022 the
FDA rejected
the BA.1 bivalent boosters because the agency felt the boosters may fall short of providing sufficient protection against the newest strains, BA.4 and BA.5, which were by then spreading quickly throughout the U.S. and the world. So the FDA asked Pfizer-BioNTech and Moderna
to develop bivalent vaccines specifically targeting BA.4 and BA.5
, instead of BA.1.
Because clinical trials are time-consuming, the
FDA was willing to consider animal studies
and other laboratory findings, such as the ability of antibodies to neutralize the virus, to decide whether to authorize the bivalent boosters.
This decision
has stirred up controversy
over whether it is appropriate for the FDA to approve a booster without direct human data to support it. However, the FDA has stated that millions of people have safely received the mRNA vaccines – which were originally tested in humans – and that the changes in the mRNA sequences in the vaccines
do not affect vaccine safety
. Thus, it concluded that the bivalent vaccines are safe and that there is no need to wait for human clinical trials.
Based on available evidence from the previous COVID-19 vaccines, we believe it is very likely that the new boosters will continue to offer strong protection from
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 only 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 initial required shots – or following a previous booster shot. The Moderna bivalent vaccine is authorized for use in people 18 years of age, while the Pfizer bivalent vaccine is authorized for those 12 years of age and older.
Because of the superiority of the bivalent vaccines, the FDA has also removed 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.
5. Will the new shots protect against future variants?
How well the bivalent vaccines will perform in the face of new variants that might arise will depend on the nature of future spike protein mutations.
If it is a minor mutation or set of mutations when compared to the original strain or to omicron variants BA.4 and BA.5, the new shots will provide good protection. However, if a hypothetical new strain were to possess highly unique mutations in its spike protein, then it’s likely that it could once again dodge immune protection.
On the flip side, the successful development of the updated vaccines demonstrates that the mRNA vaccine technology is nimble and innovative enough that – within a couple of months of the emergence of a new variant – it is now likely possible to develop and distribute new vaccines that are tailor-made to fight an emerging variant.
This article has been updated to reflect the CDC’s endorsement of the reformulated shots.