COVID-19 has taken the world by storm, and the development of vaccines has been a crucial step in curbing its spread. However, new variants continue to emerge, and maintaining immunity against the virus remains challenging. To keep the virus in check, periodic boosters may be necessary. Despite some immunity from natural infection and global vaccination, the constant emergence of new variants makes it challenging to maintain the level of immunity required to control the virus.
Washington University scientists suggest that booster shots targeting new variants can enhance population immunity. Still, the key is to target a variant different enough to trigger the production of new and diverse antibodies. Their research, published in Nature, shows that this approach can neutralize a wide range of variants, even those that have not yet emerged. Studies have shown that immunity provided by COVID-19 vaccines may wane over time, especially in the face of new variants.
Periodic booster shots can help to reignite the immune system and provide long-lasting protection against the virus. This is particularly important as new variants of the virus continue to emerge, some of which have shown to be more contagious and potentially more deadly. Boosting with either the original SARS-CoV-2 or variant-derived vaccines induces solid germinal center B cell responses in humans.
These responses persist for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Booster immunizations can generate de novo B cell responses targeting variant-specific epitopes, suggesting a naïve B cell origin.
“The whole point of making boosters against new variants is to teach the immune system to recognize features in the new variants that are different from the original strain,” Ellebedy said. “But the new variants still share many features with the original strain, and it’s possible that the response to these shared features could dominate the response to new features. The boosters could end up just engaging immune memory cells that are already present rather than creating new memory cells, which is what we need for protection against new variants.”
Researchers studied the effectiveness of COVID-19 boosters in eliciting new antibodies. They found that booster shots targeting early variants beta and delta failed to trigger the development of detectable new antibody-producing cells in 39 people who had received the two-shot primary sequence of the Pfizer/BioNTech or Moderna vaccines. However, the study found that boosters targeting the newer omicron variant successfully generated new antibodies.
“This was disappointing but not surprising,” said Ellebedy, an expert on influenza vaccines. “If you look at the beta and delta spike protein sequences, they are not very different from the original strain. If we saw this degree of difference among influenza strains, we would say there’s no reason to update the annual vaccine. But the omicron variant is a different matter.”
The Omicron variant, which carries multiple new mutations, has dominated worldwide since late 2021. Researchers gave eight people a booster explicitly targeted against the Omicron variant and found over 300 antibodies to neutralize the original strain and variants.
Six of these neutralized Omicron but not the original strain, indicating the booster successfully triggered the creation of new antibodies optimized for Omicron. One new antibody even neutralized a subvariant of Omicron that had not yet emerged when the booster was made. The CDC has since recommended updated bivalent boosters targeting Omicron and the original strain, available from Pfizer/BioNTech and Moderna since fall 2022.
“This booster engaged naive B cells and created new memory cells, which means it expanded people’s immune repertoire and equipped them to respond to a greater diversity of variants,” Ellebedy said. “Designing boosters to maintain immunity to the evolving virus will not be easy. The extent of the difference between the old and the new variants is important. But if we are careful about choosing which variants to include in boosters, I think we can stay ahead of this virus.”
In conclusion, the fight against COVID-19 is ongoing, and the need for periodic boosters is a critical aspect of maintaining immunity against the virus. As new variants emerge and immunity provided by vaccines wanes, it is important to continue research into booster shots to keep the virus in check and prevent its spread.
Journal Reference:
- Alsoussi, W.B., Malladi, S.K., Zhou, J.Q. et al. SARS-CoV-2 Omicron boosting induces de novo B cell response in humans. Nature (2023). DOI: 10.1038/s41586-023-06025-4