New scientific discovery could accelerate the success of COVID-19 vaccines

Researchers developing the COVID-19 vaccine from Oxford-AstraZeneca they identified biomarkers What they can help predict whether someone will be protected from the flat tire they receive, warns a report published in the prestigious scientific journal Nature.

The team of University of Oxford, UK, identified a “protective correlate” of the immune responses of trial participants, the first COVID-19 vaccine developer found. The identification of these blood markers, say the scientists, improve existing vaccines and accelerate the development of new vaccines reducing the need for costly large-scale efficacy trials.

“We would like to have a measurement of antibodies that is a reliable guide to protection because it could speed up the authorization of new vaccines ”, warns David Goldblatt, vaccinologist University College of London.

The news formulas of vaccines against influenza, for example, usually se judge whether they elicit a sufficiently strong antibody response against a viral protein in a relatively small number of people, rather than in large-scale trials seeking to reduce infection rates. Researchers and regulators they hope to do the same with COVID-19 vaccines.

“The power of a correlate in vaccines runs deep,” he says. Dan Barouche, Director of Beth Israel Deaconess Medical Center Virology and Vaccine Research Center in Boston, Massachusetts. “If there is a reliable correlation, then it can be used in clinical trials to make decisions about which vaccines might work, what form of vaccines might work, or how long vaccines will last. “

Search for markers

The protection is correlated usually are determined by comparing the immune responses of trial participants who were protected by a vaccine with those of ‘breakthrough cases’: volunteers who received a vaccine but were still infected.

“But due to the high efficacy of many COVID-19 vaccines, the developers took longer than expected to determine the markers of vaccine protection on the basis of revolutionary cases ”, of Peter Dull, Deputy Director of Development of integrated clinical vaccines at the Bill & Melinda Gates Foundation fr Seattle, Washington.

In the absence of groundbreaking case studies, Several teams have tried to determine a protective correlate for COVID-19 vaccines compare published data on vaccine efficacy with previous trials that measured immune responses to blows.

These studies suggest that “neutralizing” antibodies that block the virus are a good predictor of vaccine success. Those that trigger high levels of these antibodies, such as jabs Pfizer-BioNTech and Moderna, son more efficient than Oxford-AstraZeneca and Johnson & Johnson, which generated relatively low levels of neutralizing antibodies.

The Oxford-AstraZeneca study confirms the relationship between higher levels of neutralizing antibodies and protection. The analysis, conducted by the Oxford biostatistician Merryn Voysey, compared the immune responses in 171 breakthrough cases with those of over 1,404 people who received the vaccine and did not develop symptomatic infection.

Participants who had higher levels of neutralizing antibodies, as well as “binding” antibodies, which recognize the SARS-CoV-2 spike protein, they tended to get stronger protection, but not total, against symptomatic infection, the Oxford team determined. The team used a model to estimate antibody levels that corresponded to different levels of vaccine protection against COVID-19 in trials, ranging from 50% to 90% protection. Other vaccines that elicit similar antibody responses can be expected to generate similar levels of protection against symptomatic infections. say the researchers.

Miles Davenport, immunologist University of New South Wales in Sydney, Australia notes that there were no significant differences in the neutralizing antibody responses of breakthrough infections and controls. This could happen if young people at higher risk of infection, for example because they have more social contact, also had higher levels of antibodies. The Oxford team took this overlap into account in their model when estimating participants’ risk of infection. However, Couch he says that it is difficult to identify protective antibody levels based on estimated risk, rather than observed differences in antibody levels, which would only have been possible if there had been clear differences between advances and controls.

In order to Goldblatt, no it is certain that the antibody levels established in the study will predict the success of other vaccines, especially those which are based on different technologies. “We don’t want to develop something just for one vaccine or one type of vaccine,” highlighted. “We have all of these manufacturers around the world, developing vaccines based on different platforms. “

The vaccine Oxford use achimpanzee denovirus harmless to instruct cells to produce the SARS-CoV-2 spike protein, while those developed by Modern and Pfizer-BioNTech they use RNA molecules to do this. Other COVID-19 vaccines deliver the protein itself or inactivated versions of the whole SARS-CoV-2 virus.

Another team is working on correlations of protection for vaccines approved by the United States government, including those of Moderna y Johnson & Johnson. Analysis of Modern early.

Predict protection

Philippe Dormitzer, Vice-president and scientific director of viral vaccines Pfizer, he says that It is not clear whether the high levels of neutralizing antibodies explain the protection offered by the company’s vaccine. Its levels are undetectable in most people until they receive a second dose, but clinical trials and field studies suggest that the vaccine offers strong protection after a dose. The neutralizing antibodies They also do a poor job of predicting the effectiveness of the variant vaccine, he says, and their levels decline over time.

Dormitizer and other researchers warn that it is important to distinguish between biomarkers that can simply predict the success of vaccines and those that are responsible for their protective effects. In addition to neutralizing antibodies that block infection in laboratory tests, vaccines trigger antibodies with other properties, as well as T cells which kill infected cells and support other immune responses. All these pieces immune response they could have a protective role.

“Last resort, it will be up to regulators to decide how to apply the protective correlates for COVID-19 vaccines ″, indicated Dull. This is already starting to happen. The drug regulator of UK pointed out that could approve an inactivated SARS-CoV-2 vaccine, developed by the French biotechnology company Valneva, if it triggers higher antibody levels than the Oxford-AstraZeneca vaccine in a trial of 4000 participants.

Dull he says that it is important Be careful when determining and applying protective correlates to COVID-19 vaccines. If vaccines approved on the basis of a biomarker prove to be performing poorly in the real world, they could undermine vaccination efforts. But he hopes developers, regulators and stakeholders can find answers soon. “We are at a time when the ability to conduct further efficacy studies is limited. We are going to have more vaccines in the future, ”he concludes.

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