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Preventing future COVID-19 outbreaks will require frequent booster shots

As the COVID-19 pandemic continues, researchers are constantly seeking new ways to maintain immunity against the virus, particularly as it continues to mutate and produce new variants. Scientists at Washington University School of Medicine in St. Louis have published research in the journal Nature indicating that updated booster shots could be key in maintaining population immunity, but there’s a catch.

Although natural infection and widespread vaccination have provided some immunity against COVID-19, the virus is constantly evolving and producing new variants that can partially evade antibodies produced by vaccines and prior infections. To maintain population immunity, it’s essential to update booster shots, but the challenge lies in designing a shot that can elicit a broad antibody response capable of neutralizing a wide array of variants, including those that have not yet emerged.

“The challenge with COVID-19 is that the virus keeps mutating,” said study senior author Dr. Ali Ellebedy. “It’s not that the vaccines don’t elicit a lasting antibody response. They do. The problem is that the virus changes and the existing antibodies become irrelevant. Here we showed that it’s possible to design a variant-specific booster that doesn’t just strengthen the antibodies people already have but elicits new antibodies. This means that periodically giving boosters targeting new variants would allow population-level protection to be maintained even as the virus evolves.”

The first COVID-19 vaccines were highly effective, reducing the risk of severe illness and death by over 90 percent. However, as the virus mutated, the antibodies produced by the vaccines became less effective at recognizing and neutralizing emerging variants, leading to breakthrough infections. Updating the vaccines to target new variants was an obvious solution, but the success of the first vaccines made designing an effective variant booster shot tricky.

“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,” said Dr. Ellebedy. “But the new variants still share a lot of 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.”

The researchers found that vaccinating individuals with the original strain of the virus and then boosting them with a shot targeting a new variant can elicit a broad antibody response capable of neutralizing a wide array of variants, including those that have not yet emerged. The key is to target a variant that is so different from the original strain that it triggers the maturation of new and diverse antibody-producing cells.

This research provides important insights into how to maintain population immunity against COVID-19, particularly as the virus continues to evolve and produce new variants. By designing booster shots that elicit new and diverse antibody-producing cells, researchers can help ensure that population-level protection is maintained, even as the virus evolves.

Dr. Ellebedy and colleagues conducted a study to determine the efficacy of boosters in producing new antibodies. The study involved individuals who received a COVID-19 vaccine targeted at the original strain, followed by either a combined booster targeting the beta and delta variants or a booster targeting the omicron variant. 

The initial findings were not promising, as noted by Ellebedy. The study examined 39 participants who had received the Pfizer/BioNTech or Moderna COVID-19 vaccines’ two-shot primary sequence, followed by an experimental booster targeted at the beta and delta variants. While all participants produced antibodies that neutralized the original virus strain and the beta and delta variants, none of the antibodies detected were specific to beta or delta. According to Dr. Ellebedy, the absence of such antibodies suggested that the variant booster had failed to activate the development of detectable new antibody-producing cells.

“This was disappointing but not surprising… If you look at the sequences for the beta and delta spike proteins, they are not really very different from the original strain,” said Dr. Ellebedy. “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.”

In contrast to the earlier boosters, which targeted the beta and delta variants, the omicron-targeted booster was more successful. Eight individuals who had received the Pfizer/BioNTech or Moderna COVID-19 vaccine were recruited, and a booster targeting only the omicron variant was administered. The CDC later recommended bivalent boosters that targeted both the omicron variant and the original strain, and these became available to the public in fall 2022, produced by both Pfizer/BioNTech and Moderna.

The researchers collected blood samples from the participants four months after their boosters and identified more than 300 distinct antibodies capable of neutralizing the original strain or one or more of the variants. Six of these antibodies neutralized omicron but not the original strain, indicating that the booster had successfully activated the creation of new antibodies optimized for omicron. One of these new antibodies even neutralized BA.5, a subvariant of omicron that is currently circulating widely but had not yet emerged when the booster was created.

“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,” said Dr. Ellebedy. “The extent of the difference between the old and the new variants is clearly important. But if we are careful about how we choose which variants to include in boosters, I think we can stay ahead of this virus.”

The COVID-19 pandemic has drastically changed the way people live their lives around the world. As of April 2023, the virus has infected over 500 million people and caused more than 10 million deaths globally. COVID-19 is caused by the novel coronavirus SARS-CoV-2, which was first identified in Wuhan, China, in December 2019. Since then, the virus has spread rapidly across the globe, prompting governments to implement strict measures to limit its spread.

SARS-CoV-2 is a member of the Coronaviridae family, which also includes the viruses that cause SARS and MERS. Like other coronaviruses, SARS-CoV-2 is a positive-sense, single-stranded RNA virus that infects host cells by binding to ACE2 receptors. The virus is primarily transmitted through respiratory droplets when an infected person talks, coughs, or sneezes.

COVID-19 can cause a wide range of symptoms, from mild to severe, and may even be asymptomatic. The most common symptoms include fever, cough, and shortness of breath, but other symptoms such as fatigue, muscle aches, headache, loss of taste or smell, sore throat, and congestion may also be present. Severe cases of COVID-19 can lead to acute respiratory distress syndrome (ARDS), which can be fatal.

Currently, there is no cure for COVID-19, and treatment mainly focuses on managing symptoms and preventing complications. Mild cases can be managed with rest, fluids, and over-the-counter medications to relieve symptoms such as fever and cough. Severe cases may require hospitalization, supplemental oxygen, and in some cases, mechanical ventilation. In addition, some antiviral drugs and monoclonal antibodies have been authorized for emergency use to treat COVID-19 in specific populations.

The development and distribution of COVID-19 vaccines have been a significant breakthrough in the fight against the pandemic. The vaccines work by stimulating the immune system to recognize and fight the virus, providing protection against severe disease and hospitalization. Multiple vaccines have been authorized for emergency use by regulatory agencies worldwide, including Pfizer-BioNTech, Moderna, AstraZeneca, and Johnson & Johnson. Vaccination campaigns have been launched globally to reach as many people as possible.

Preventing the spread of COVID-19 is crucial to controlling the pandemic. Basic preventive measures include wearing masks, social distancing, washing hands frequently, and avoiding large gatherings. Governments and health organizations around the world have also implemented additional measures, such as lockdowns, travel restrictions, and quarantine requirements, to limit the spread of the virus.

The COVID-19 pandemic has had a profound impact on the world, and the fight against the virus is ongoing. While vaccination campaigns offer hope for controlling the spread of the virus, it is crucial to continue to practice basic preventive measures and follow public health guidelines to protect ourselves and those around us. Ongoing research into the virus and its effects will also be essential in developing effective treatments and strategies to prevent future pandemics.


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