Booster needed to neutralize the fast-spreading variant

  • Traditional COVID-19 vaccine regimens do not neutralize the fast-spreading Omicron variant according to a study from MGH, MIT and Harvard.
  • People who received three doses of the mRNA vaccine had very strong neutralization against the Omicron variant, as opposed to those who received two doses.

An additional “booster” dose of Moderna or Pfizer mRNA vaccine is needed to provide immunity against the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, according to a study by researchers from the Ragon Institute of MGH, MIT and Harvard. The results of this study, reported in the journal Cell, indicate that traditional COVID-19 vaccine regimens available in the United States do not produce antibodies capable of recognizing and neutralizing the Omicron variant.

In late November, health officials in South Africa reported that a previously unknown variant of SARS-CoV-2 was rapidly spreading across the country. The variant, dubbed Omicron by the World Health Organization, would soon prove to be much more transmissible than Delta, the variant that previously caused the majority of COVID-19 infections. “People desperately wanted to know if current vaccines protect against Omicron,” says lead author of the Cell paper, Alejandro Balazs, whose lab at the Ragon Institute studies how to engineer immunity against infectious diseases.

To find answers, Balazs collaborated with a team that included the Cell paper’s lead author, Wilfredo F. Garcia-Beltran, a clinical pathology resident at the MGH and a clinician scientist at the Ragon Institute. The first step was to construct a harmless version of Omicron known as a “pseudovirus” that could be used in the laboratory to assess the effectiveness of the three COVID-19 vaccines available in the United States, which include the two doses Pfizer and Moderna injections and the Johnson & Johnson single-dose vaccine. The pseudovirus that Balazs and his colleagues created mimicked the behavior of Omicron, which has 34 mutations on its “spike” protein that are not found on the original strain of SARS-Cov-2 first detected in Wuhan, China. China, in December 2019. Scientists believe that these mutations may be partially responsible for the rapid spread of Omicron across the world.

Next, Garcia-Beltran worked with MGH colleagues, including hematology-oncology colleague Vivek Naranbhai, to acquire blood samples from 239 people who had been fully vaccinated with one of the three COVID-19 vaccines. Study subjects included employees of Massachusetts’ General Brigham Health System and residents of Chelsea, Massachusetts, a community with a high rate of COVID-19 infections. “It was important for us to have a diverse population represented in the study,” says Garcia-Beltran. This group included 70 men and women who had received a third booster dose of the Pfizer or Moderna vaccine, according to recommendations from the Centers for Disease Control and Prevention.

COVID-19 booster doses per capita in selected countries.

COVID-19 booster doses per capita in selected countries.

Image: Our World in Data

The blood samples were used to measure how effectively each vaccine induces the production of protective immunity in the form of antibodies against the Omicron pseudovirus, as well as Delta and wild-type viruses. The results were startling. “We detected very little neutralization of the Omicron variant pseudovirus when we used samples taken from people recently vaccinated with two doses of mRNA vaccine or one dose of Johnson & Johnson,” says Balazs. “But individuals who received three doses of mRNA vaccine had highly significant neutralization against the Omicron variant.”

It’s not yet clear why an mRNA boost significantly improves immune protection against Omicron, but Garcia-Beltran says one possibility is that an extra dose creates antibodies that bind more tightly to the spike protein, thereby increasing their effectiveness. Additionally, a booster dose can generate antibodies that target regions of the spike protein that are common to all forms of SARS-CoV-2. Both theories may be true, says Garcia-Beltran.

In 2000, Gavi, the Vaccine Alliance was launched at the annual meeting of the World Economic Forum in Davos, with an initial commitment of $750 million from the Bill and Melinda Gates Foundation.

Gavi’s goal is to make vaccines more accessible and affordable for everyone, wherever people live in the world.

In addition to saving an estimated 10 million lives worldwide in less than 20 years by vaccinating nearly 700 million children, – Gavi recently provided a life-saving Ebola vaccine.


At Davos 2016, we announced Gavi’s partnership with Merck to make the life-saving Ebola vaccine a reality.

The Ebola vaccine is the result of years of energy and commitment from Merck; the generosity of the federal government of Canada; leadership by WHO; strong support to test the vaccine from NGOs such as MSF and countries affected by the outbreak in West Africa; and the rapid response and dedication of the DRC Minister of Health. Without these efforts, this vaccine is unlikely to be available for several years, if at all.

Learn more about the Vaccine Alliance and how you can help improve access to vaccines around the world – in our Impact Story.

Balazs notes that the three-dose mRNA vaccine regimen — that is, the traditional two doses and a booster of the Pfizer or Moderna vaccines — provides slightly lower levels of neutralizing antibodies against Omicron than it does. made against the wild-type strain COVID-19 or the Delta variant. But the study results strongly support the CDC’s advice that COVID-19 booster shots are suitable for anyone 16 and older, and that mRNA vaccines are preferred.

Balazs is a principal investigator at the Ragon Institute and an assistant professor of medicine at Harvard Medical School. Garcia-Beltran recently created her own laboratory at the Ragon Institute.


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