Newly developed vaccine provides superior protection against omicron variants

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Yale scientists have developed a new omicron-specific mRNA vaccine that provides superior immune protection against two viral subvariants compared to standard mRNA vaccines.

The new vaccine, called Omnivax, increased the neutralizing antibody response against the BA.1 and BA.2.12.1 omicron subvariants in pre-immunized mice by 19-fold and eight-fold, respectively, compared to mRNA vaccines standard. The improved response against the BA.1 subvariant was reported on June 6 in the review Nature Communication. The results of the study involving the BA.2 subvariant were published July 19 in the journal Cell discovery.

“While standard mRNA vaccines still provide protection against infection by new variants, their efficacy declines over time and has been compromised due to immune mutations escaping emerging variants,” said Sidi Chen, associate professor of genetics at the Yale School of Medicine and senior author of both. studies. “We wanted to see if we could develop variant-specific vaccines that provide additional protection against emerging subvariants.”

The experimental vaccines, developed in Chen’s lab by a team led by postdoctoral associate Zhenhao Fang, use engineered lipid nanoparticles to deliver mRNA to cells with “instructions” to create spike proteins from variants mutants, which the virus uses to attach to and infect cells. The presence of these foreign viral fragments prompts the immune system to create antibodies against the virus. Rapidly mutating spike proteins on the surface of the virus over time created a parade of subvariants and allowed them to blunt the protection of previous generations of mRNA vaccines developed by Moderna and Pfizer-BioNTech.

Modified lipid nanoparticle mRNA vaccines can be created quickly, the researchers say. For example, the BA.1 subvariant appeared in mid-November; by mid-December, Yale researchers had developed a vaccine against the new strain. However, testing of the vaccine’s effectiveness in mice and a peer review of the study were not completed until February. By March, the BA.2 subvariant had established itself as the predominant strain circulating in most of the world. The researchers then investigated whether the omicron variant vaccine retained its superiority over standard vaccines against BA.2. The new vaccine also stimulated a superior immune response to standard vaccines in mice against this subvariant, researchers reported in the Cell discovery paper.

“While translating the novel vaccine candidate from bench to bedside requires rigorous testing in human trials, these preclinical studies provide a comprehensive and unbiased evaluation of an omicron-specific vaccine candidate, which will hopefully , will fuel the development of next-generation COVID vaccines,” Chen said. said.

In light of the rise of the new BA.4 and BA.5 variants, which have become the most common among COVID cases, Yale researchers are now testing a new candidate vaccine against these variants in mice.

“We have a system in place to combat these emerging subvariants, but we need to adjust the system to respond more quickly to emerging health threats,” Chen said.

Chen is affiliated with Yale Cancer Center, Yale Stem Cell Center, Yale Center for Biomedical Data Science, and Systems Biology Institute and Center for Cancer Systems Biology at Yale West Campus.

Zhenhao Fang and Lei Peng of Yale are co-first authors of both papers. Chen is the corresponding author of both articles. Craig Wilen, assistant professor of laboratory medicine and immunobiology at Yale, is the corresponding co-author of Nature Communication paper.


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More information:
Zhenhao Fang et al, Heterotypic vaccine responses against SARS-CoV-2 Omicron BA.2, Cell discovery (2022). DOI: 10.1038/s41421-022-00435-w

Zhenhao Fang et al, Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2, Nature Communication (2022). DOI: 10.1038/s41467-022-30878-4

Provided by Yale University

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