How blood samples are helping scientists test COVID-19 vaccines against Omicron

Vaccine makers including Pfizer Inc. and Moderna Inc., as well as US government and academic scientists, are racing to run lab tests expected to answer. Most laboratories expect results in a few weeks, although a South African research institute said on Tuesday that early findings from laboratory tests showed that the vaccines from Pfizer and BioNTech SE protected against infection against the Omicron variant compared to its performance. One-forty-fifth of the fighting antibodies are generated. Original version of the virus.

The answers can help determine whether companies need to roll out modified booster shots that specifically target the Omicron variant, or if existing shots will suffice.

“If we get an early look in a couple of weeks, this is a significant effort,” said Dr. Kathleen Neuzil, director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine. of Covid-19 vaccines. “It’s still a scramble and a lot of work.”

An important part of the effort to assess vaccines is for scientists to collect blood samples — specifically, serum, the part of the blood that remains after it’s frozen — previously taken from people who have had clinical trials. Received Kovid-19 vaccines in trials or from actual. World use of vaccines.

Most of the thousands of people enrolled in these studies starting last year gave blood samples before and after vaccination so researchers could analyze changes in immune-system antibodies. Various clinical-trial sites, companies and government scientists have collected samples.

Now scientists are using these same samples to run tests in Petri-type dishes, and the samples are proving useful as new types have emerged, the latest being Omicron. “The fact that we have this bank of samples is working in our favor,” Dr. Nuzil said.

“We’re looking increasingly to test sera from people who have been vaccinated with our vaccine, as is every other manufacturer,” Moderna president Stephen Hoge said at an investor conference on December 1.

Another key component of these tests: modified versions of the coronavirus, known as pseudoviruses. They are engineered to resemble a live omicron virus, but do not replicate, so they are safe to handle in laboratories.

Researchers mix blood samples with Omicron pseudoviruses in laboratory dishes and incubate them. They add cells from human cell lines – such as human kidney cells that are grown in batches in a lab for research purposes – into the mixture, to see if pseudoviruses are able to get inside cells, or whether vaccines are available. -induced antibodies block them.

The pseudovirus also contains an enzyme called luciferase, which makes firefly glow, and which helps researchers track the effect of antibodies on the pseudovirus.

Luciferase allows researchers to visualize the virus and see if it gets into cells. Machines called luminometers, which are the size of a desktop computer, measure luminescence in cells and determine whether pseudovirus is entering cells, and by how much, says director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Dan Baruch said. Medical Center in Boston. His lab is running these tests on the serum of people vaccinated with the Johnson & Johnson shot — which he helped design — as well as shots from Pfizer and Moderna.

Some laboratories are also running live-virus tests with omicrons and blood samples with necessary biosafety precautions, as with South Africa’s research released on Tuesday. But scientists have found that the results of pseudovirus tests are generally consistent with those using live viruses.

Pseudoviruses include genetic mutations found in the spike protein on the surface of the Omicron virus variant. The spike protein is the main target of COVID-19 vaccines in triggering the immune response.

Most laboratories need to order synthetic genes with coding for the Omicron spike protein from outside suppliers, and then take several days to create a pseudovirus, said John Mascola, director of the Vaccine-Research Center at the National Institute of Allergy and Infectious Diseases. seem. Disease. The institute is also testing COVID-19 vaccines against Omicron.

Blood-sample test results are likely to predict how vaccines hold against Omicron, but they will have limitations, Dr. Muskola said.

Scientists will also assess other elements of the immune response induced by the vaccines in addition to antibody production, but those tests could take longer.

More definitive answers about the activity of vaccines against Omicron will come later, when researchers look at how well the vaccines protect against Omicron in vaccinated people, not laboratory dishes. They will be able to see whether people who have been vaccinated are getting breakthrough infections or serious disease at a higher rate than other types.

Norwegian officials said they have seen a few cases of the Omicron variant in vaccinated people, but most have been exceedingly mild. However, scientists say it is too early to determine whether the level of reported disease severity is associated with age, prior infection, vaccination, or some property of Omicron.

Health officials in South Africa identified the Omicron variant in late November, and have since been detected in several other countries, including the US, with the World Health Organization saying the variant is at increased risk of reinfection compared to other variants. could. There have been early indications that Omicron is highly transmitted, but may cause milder disease than initially suspected; Health officials are still exploring these questions.

The Omicron variant has an unusually high number of mutations compared to previous strains, raising concerns that it may evade the immunity conferred by vaccines. Most of the COVID-19 vaccines were designed to target the coronavirus strain that emerged in China and was dominant during 2020.

William Moss, executive director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public, said it is possible that COVID-19 vaccines will be less effective at preventing Omicron infection, but will maintain their effectiveness against serious disease caused by the virus. . Health. This can happen when vaccines induce insufficient immune-system antibodies against an infection, but still mobilize the immune system’s “memory response” that prevents the infection from getting worse, he said.

Vaccine makers and government officials partly relied on tests of blood samples earlier this year to conclude that the vaccines had neutralizing activity against the highly permeable delta variant, but that strain caused were still sufficient to provide protection against serious illness.