Vaccines targeting Omicron are not better than the original jabs in early testing

As the Omicron variant of SARS-CoV-2 continues to rampage globally, vaccine makers are devoting resources to clinical trials of COVID-19 shots tailored to highly infectious variants. However, much of the early animal research Omicron-specific booster No advantage over the third dose of the current vaccine^{1– –Four}..

Most studies have targeted only a small number of animals, with only eight primates in one case and no peer-reviewed. However, they provide early hints that a single dose of a customized vaccine will not change the game against Omicron.

“The findings from these preclinical studies in animal models are that boost immunization with variant vaccines is actually less effective than booster immunization with current vaccines,” said the director of the AIDS Vaccine Institute. Said David Montefiori. Research and development at Duke University Medical Center in Durham, North Carolina, researching the COVID-19 vaccine.

The quest for custom vaccines

Because it was First identified In November, Omicron became the predominant variant in the world.this is biology It is very different from the original “ancestor” strain of SARS-CoV-2, which is the basis of the currently approved vaccine.Differences may explain why the three doses of existing vaccines are Low efficacy Against Omicron than against other variants.

Changes in the virus have forced manufacturers of widely used mRNA-based vaccines to develop. Omicron-compatible formulation.. Pfizer and Moderna announced in late January that they had begun clinical trials of Omicron-specific jabs. These should give you data for the coming months.

While scientists wait for results, animal studies published as preprints provide an early glimpse into the potential usefulness of these updated vaccines.

One study¹ The immune response of eight rhesus monkeys was examined (Rhesus monkey) If you have been vaccinated 3 times: If you have been vaccinated twice with Moderna’s original vaccine, amplifier Either the same shot or a version incorporating Omicron’s highly mutated spike protein that the virus uses to invade human cells. The authors found that monkeys boosted with either vaccine showed a wide range of antibody responses to all variant of concern, including Omicron.

Importantly, boosters also had a positive effect Memory B cells, Responsible for cranking out the antibody to dodge the virus. Both the original vaccine and the renewed jab promoted elevated levels of animal “cross-reactive” memory B cells. It targets many mutants, not just those found in vaccines.

“For now, that’s a very good thing,” said Robert Cedar, co-author of this paper and immunologist at the National Institute of Infectious Diseases in Bethesda, Maryland. “That means that the current vaccine boost can still cover all known variants.” However, he warns that the study only examined the immune response up to 4 weeks after boosting, saying it is not clear how long the increase in antibody production will continue.

Booster vs Booster

Cedar’s group also exposed Omicron to boost-immunized animals with either the original vaccine or a version compatible with Omicron. “Both boosts completely shut down virus replication within two days,” he says. In both this experiment and the experiment analyzing memory B cell responses, the omicron-specific vaccine showed no significant advantage over the original vaccine.

The study of eight animals is not definitive. But given the condensed pandemic-style timescale, this study is worth it, says Montefiori.

Study in line with primate results² In mice, giving an omicron-matched boost after two doses of the mRNA-based vaccine was found to provide less benefit than standard boost. The study also looked at omicron-specific vaccines in “naive” mice (previously unimmunized mice) and found that rodents produce high levels of potent antibodies against omicrons. However, these antibodies had limited ability to inhibit other major variants of COVID-19.Another study³ Similar results were reported in naive mice immunized with an Omicron-compatible mRNA vaccine.

Fourth study^Four The “replicated RNA” vaccine was investigated. In contrast to the widely used mRNA vaccine, this encodes both a viral snippet and an enzyme that amplifies the expression of that snippet. Scientists inoculated mice three times with the replication RNA vaccine produced by HDT Bio in Seattle, Washington. Two doses based on the ancestral SARS-CoV-2 strain, followed by a single Omicron-specific booster.

The third dose did not show an increased immune response to Omicron. However, such a response was seen in mice that received a single dose of the ancestral lineage-based vaccine and two doses of the Omicron-specific vaccine.

“These studies teach us the rules of immune system involvement when boosting with a mutant vaccine,” says Montefiori. These rules suggest that a single booster of a mutant-compatible vaccine is probably not the solution, he says. “There are still important questions that need to be addressed. Hopefully Pfizer and Moderna’s human Omicron studies will do that.”