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Pancoronavirus vaccine may be the key to fighting future pandemics

Pancoronavirus vaccine may be the key to fighting future pandemics


Editor’s Note: Find the latest COVID-19 news and guidance from Medscape Coronavirus Resource Center.

As the COVID-19 pandemic disappears, efforts are being stepped up to develop next-generation vaccines that can protect against future new coronaviruses and variants, at least for the foreseeable future. Some projects present a clever combination of viral parts to the immune system, evoking a powerful and hopefully persistent response.

The next-generation “bread” vaccine aims to limit SARS-CoV-2, its relatives, and potential outbreaks to more domesticated respiratory viruses such as the common cold. It is said that. Whatever the ultimate component of this new generation of vaccines, experts agree with the goal of preventing severe illness and death. And a broader approach is important.

“All the vaccines were great. But we’re playing a Whac-A-Mole game with variants. We need to take a step back and ask if a panvariant vaccine is possible. Omicron isn’t, so that’s it. It’s important. The last variant. ” Dr. Jacob Lemie, an instructor of medical and infectious disease specialists at Massachusetts General Hospital, said.

Broad-spectrum vaccine

There was an early desire among many researchers to create a vaccine that would block multiple coronaviruses.Ann The article has been published of Nature By researchers at the National Institute of Allergy and Infectious Diseases (NIAID) in May 2020 Luca T. JurgaMD, and colleagues said it all in the title: Universal Coronavirus Vaccine: Now is the time to start.

What are their concerns? The diversity of bat coronaviruses is ready to dive into humans. High variability of spike genes recognized by immune response. Persistent mutations in RNA virus that cannot repair errors.

Research on a broader vaccine began in several laboratories as SARS-CoV-2 produced the mutant after the mutant.

On September 28, NIAID announced funding for the development of the “Pan Coronavirus” vaccine. The quotes indicate that the magic bullet against the new coronavirus is unrealistic. “These new awards aim to anticipate and prepare for the next generation of potentially pandemic coronaviruses,” said Dr. Anthony Fauci, director of NIAID. The first three awards were given to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned NIAID funding in his State of the Union address. He also led the development of new vaccine platforms and vaccines targeting a wider range of pathogens by the Biomedical Advanced Research and Development Agency (BARDA), which was established in 2006 to prepare for public health emergencies. I also talked about how to do it.

Meanwhile, individual researchers in the eclectic field are finding new ways to prevent future pandemics.

Dr. Artem Babaian, a computational biologist at the University of Cambridge, had the idea of ​​looking back at the National Institutes of Health’s (NIH) genomic database for overlooked new coronaviruses, dating back more than a decade. .. He started a project between his jobs when the pandemic was widespread and used a telltale enzyme specific to the RNA virus to catch COVID’s cousin.Job is Was announced in Nature Data freely available in and

Of the approximately 132,000 new RNA viruses discovered by Baban’s team, nine were from previously unrecognized coronaviruses. Novel 9 comes from “ecologically diverse sources” such as seahorses, axolotl, eels, and some fish. Decoding the terrain of these coronaviruses may provide clues for developing vaccines that are ahead of future pandemics.

However, optics are important to keep expectations reasonable. “” Universal vaccine “is a misnomer. I consider it a “widespread vaccine”. It is important to know in advance that these vaccines can never guarantee immunity to all coronaviruses. There is nothing absolute in biology, but we hope it works for the dangers we know. Vaccines that mimic exposure to many coronaviruses can protect against current coronaviruses.It contains an unknown coronavirus, especially a slow-evolving antigen, “Babaian said. Medscape Medical News..

Nikolai Petrovsky, a doctor of medicine at Flinders University School of Medicine and Public Health in Adelaide, Australia, and Pty Ltd, a biotechnology company vaccine, agree to literally call the Pancorona virus vaccine a “pipe dream.” Defensive Pan-CoV-19 Vaccine — We have already developed and tested it, so we can say that we are combining antigens rather than trying just one that can do everything. “

Immunity lure

A wider range of vaccines under development will display viral antigens such as peplomers in the immune system of various frameworks. Here are some approaches.

Ferritin nanoparticles: A candidate vaccine from the Emerging Infectious Diseases Branch of the Waterlead National Military Medical Center began Phase 1 human trials in April 2021. The vaccine, called SpFN, consists of an array of ferritin nanoparticles linked to various mutants and species of peplomer. Ferritin is a protein that binds to and stores iron in the body.

“The repetitive and orderly display of coronavirus spike proteins on multifaceted nanoparticles can stimulate immunity in ways that lead to very broad protection,” said Walter Reed. Kayvon Modjarrad, MD, PhD, co-inventor of the vaccine, said.

The second vaccine targets only the “bull’s eye” portion of the spike that the virus uses to attach and access human cells. This is called the receptor binding domain (RBD) and is the virus behind the SARS-CoV-2 mutant and the original virus. SARS.Preclinical data Appeared in Scientific translation medicine..

Dr. Burton Haynes and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-beta coronavirus vaccine” that refers to the genus to which SARS-CoV-2 belongs. They say their result in macaques, As published in Nature, “Show that current mRNA-based vaccines may provide some protection from future outbreaks of the zoonotic betacoronavirus.”

Mosaic nanoparticles : Graduate student Alexander Cohen is leading the effort to use nanoparticles of bacterial protein in the laboratory of PhD, Pamela Bjorkman, California Institute of Technology (“Streptococcus pyogenes) RBD from 4 or 8 different betacoronavirus peplomer proteins is attached. This strategy shows that the whole is greater than the sum of the parts.

“Alex’s results show that coronavirus strains not represented in the injected nanoparticles can also trigger a variety of neutralizing antibody reactions. This technique invades humans. We hope it can be used to protect against future animal coronaviruses. ” Björkman.the work Appeared in Chemistry..

Candidate vaccines from Inovio Pharmaceuticals also use the mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and has been tested against Omicron. Also, another version of “pan-COVID-19” coverage has been thoroughly tested on animal models. Inovio vaccines are delivered to the skin using a special device that applies electrical pulses that increase the permeability of cells.

Chimera spikes: Yet another approach is to make vaccines from different parts of the beta coronavirus most closely related to SARS-CoV-2-MERS and the pathogens behind SARS, and some bat viruses and some. Bat virome virus. The abundance and ubiquity of these viruses provides a kind of toolbox with written instructions in RNA language for vaccine selection, analysis, recombination, and customization.

“Viruses like SARS can recombine in some parts of the genome to show great genetic diversity. We designed chimeric spikes to improve the coverage of multiple vaccines,” said Dr. David Martinez. Says.

His team at the University of North Carolina at Chapel Hill has developed an mRNA vaccine that provides not only RBD but also “scrambled coronavirus spikes” that represent different parts.As explained in, Chemistry Last August.

In mice, chimeric vaccines elicit a potent T and B cell immune response, stimulate antibody production, and control other aspects of immune construction.

Beyond Spike Bullseye

The challenge of developing a pancoronavirus vaccine is double. “The best vaccines are very specific to each strain, and universal vaccines have to sacrifice efficacy to get a wide range. Life is a trade-off,” Petrovsky said. Medscape Medical News..

Efforts to expand vaccine efficacy ventures beyond targeting the receptor-binding domain bulge of spike triplets that make the virus a flower class. Some projects have focused on less variable spikes that are more similar among coronaviruses that are less closely related than the mutagenic RBD. For example, peptides that twist into the “stem helix” portion of the spike that attaches to the host cell are the basis of some candidate vaccines currently in preclinical studies.

Yet other vaccines are not spike-based. For example, the French company Osivax is working on a vaccine that targets the nucleocapsid protein that protects viral RNA. By presenting different aspects of the pathogen, it is expected to stimulate immunity beyond the initial antibody rush and elicit a more diverse and sustained T cell response.

Science seems to have finally learned from history, with countless efforts to back up the first-generation COVID-19 vaccine with new vaccines that provide broader protection.

“After the SARS outbreak, we lost interest and couldn’t complete the development of a vaccine to use in case of recurrence. Don’t make the same mistake again,” Giurgea et al. Write. Nature Articles about Universal Coronavirus Vaccine.

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