Amazing Science

Software from Baidu Research yields jabs for COVID that have greater shelf stability and that trigger a larger antibody response in mice than conventionally designed shots. An artificial intelligence (AI) tool that optimizes the gene sequences found in mRNA vaccines could help to create jabs with greater potency and stability that could be deployed across the globe. Developed by scientists at the California division of Baidu Research, an AI company based in Beijing, the software borrows techniques from computational linguistics to design mRNA sequences with more-intricate shapes and structures than those used in current vaccines. This enables the genetic material to persist for longer than usual. The more stable the mRNA that’s delivered to a person’s cells, the more antigens are produced by the protein-making machinery in that person’s body. This, in turn, leads to a rise in protective antibodies, theoretically leaving immunized individuals better equipped to fend off infectious diseases. What’s more, the enhanced structural complexity of the mRNA offers improved protection against vaccine degradation. During the COVID-19 pandemic, mRNA-based shots against the SARS-CoV-2 coronavirus famously had to be transported and kept at temperatures below –15°C to maintain their stability. This limited their distribution in resource-poor regions of the world that lack access to ultracold storage facilities. A more resilient product, optimized by AI, could eliminate the need for cold-chain equipment to handle such jabs. The new methodology is “remarkable”, says Dave Mauger, a computational RNA biologist who previously worked at Moderna in Cambridge, Massachusetts, a maker of mRNA vaccines. “The computational efficiency is really impressive and more sophisticated than anything that has come before.”

Linear thinking

Vaccine developers already commonly adjust mRNA sequences to align with cells’ preferences for certain genetic instructions over others. This process, known as codon optimization, leads to more-efficient protein production. The Baidu tool takes this a step further, ensuring that the mRNA — usually a single-stranded molecule — loops back on itself to create double-stranded segments that are more rigid (see ‘Design optimization’). Known as LinearDesign, the tool takes just minutes to run on a desktop computer. In validation tests, it has yielded vaccines that, when evaluated in mice, triggered antibody responses up to 128 times greater than those mounted after immunization with more conventional, codon-optimized vaccines. The algorithm also helped to extend the shelf stability of vaccine designs up to sixfold in standard test-tube assays performed at body temperature. “It’s a tremendous improvement,” says Yujian Zhang, former head of mRNA technology at StemiRNA Therapeutics in Shanghai, China, who led the experimental-validation studies. So far, Zhang and his colleagues have tested LinearDesign-enhanced vaccines against only COVID-19 and shingles in mice. But the technique should prove useful when designing mRNA vaccines against any disease, says Liang Huang, a former Baidu scientist who spearheaded the tool’s creation. It should also help in mRNA-based therapeutics, says Huang, who is now a computational biologist at Oregon State University in Corvallis. The researchers reported their findings on 2 May in Nature1.

Optimal solutions

Already, the tool has been used to optimize at least one authorized vaccine: a COVID-19 shot from StemiRNA, called SW-BIC-213, that won approval for emergency use in Laos late last year. Under a licensing agreement established in 2021, the French pharma giant Sanofi has been using LinearDesign in its own experimental mRNA products, too. Executives at both companies stress that many design features factor into the performance of their vaccine candidates. But LinearDesign is “certainly one type of algorithm that can help with this”, says Sanofi’s Frank DeRosa, head of research and biomarkers at the company’s mRNA Center of Excellence. Another was reported last year. A team led by Rhiju Das, a computational biologist at Stanford School of Medicine in California, demonstrated that even greater protein expression can be eked out of mRNA — in cultured human cells at least — if certain loop patterns are taken out of their strands, even when such changes loosen the overall rigidity of the molecule2. That suggests that alternative algorithms might be preferable, says theoretical chemist Hannah Wayment-Steele, a former member of Das’s team who is now at Brandeis University in Waltham, Massachusetts. Or, it suggests that manual fine-tuning of LinearDesign-optimized mRNA could lead to even better vaccine sequences. But according to David Mathews, a computational RNA biologist at the University of Rochester Medical Center in New York, LinearDesign can do the bulk of the heavy lifting. “It gets people in the right ballpark to start doing any optimization,” he says. Mathews helped develop the algorithm and is a co-founder, along with Huang, of Coderna.ai, a start-up based in Sunnyvale, California, that is developing the software further. Their first task has been updating the platform to account for the types of chemical modification found in most approved and experimental mRNA vaccines; LinearDesign, in its current form, is based on an unmodified mRNA platform that has fallen out of favour among most vaccine developers.

A structured approach

But mouse studies and cell experiments are one thing. Human trials are another. Given that the immune system has evolved to recognize certain RNA structures as foreign — especially the twisted ladder shapes within many viruses that encode their genomes as double-stranded RNA — some researchers worry that an optimization algorithm such as LinearDesign could end up creating vaccine sequences that spur harmful immune reactions in people. “That’s kind of a liability,” says Anna Blakney, an RNA bioengineer at the University of British Columbia in Vancouver, Canada, who was not involved in the study. Early results from human clinical trials involving StemiRNA’s SW-BIC-213 suggest the extra structure is not a problem, though. In small booster trials reported so far, the shot’s side effects have proved no worse than those reported with other mRNA-based COVID-19 vaccines3. But as Blakney points out: “We’ll learn more about that in the coming years.”

Research Cited published in Nature (May 2, 2023):

https://doi.org/10.1038/s41586-023-06127-z 

An Australian company resurrects flesh of lost species to demonstrate potential of meat grown from cells as food source. Recently, they created a mammoth meatball, resurrecting the flesh of the long-extinct animals. The project aims to demonstrate the potential of meat grown from cells, without the slaughter of animals, and to highlight the link between large-scale livestock production and the destruction of wildlife and the climate crisis. The mammoth meatball was produced by Vow, an Australian company, which is taking a different approach to cultured meat. There are scores of companies working on replacements for conventional meat, such as chicken, pork and beef.

But Vow is aiming to mix and match cells from unconventional species to create new kinds of meat. The company has already investigated the potential of more than 50 species, including alpaca, buffalo, crocodile, kangaroo, peacocks and different types of fish. The first cultivated meat to be sold to diners will be Japanese quail, which the company expects will be in restaurants in Singapore this year. “We have a behaviour change problem when it comes to meat consumption,” said George Peppou, CEO of Vow . “The goal is to transition a few billion meat eaters away from eating [conventional] animal protein to eating things that can be produced in electrified systems.

“And we believe the best way to do that is to invent meat. We look for cells that are easy to grow, really tasty and nutritious, and then mix and match those cells to create really tasty meat.” Tim Noakesmith, who cofounded Vow with Peppou, said: “We chose the woolly mammoth because it’s a symbol of diversity loss and a symbol of climate change.”

The creature is thought to have been driven to extinction by hunting by humans and the warming of the world after the last ice age. The initial idea was from Bas Korsten at creative agency Wunderman Thompson: “Our aim is to start a conversation about how we eat, and what the future alternatives can look and taste like. Cultured meat is meat, but not as we know it.” Plant-based alternatives to meat are now common but cultured meat replicates the taste of conventional meat.

Cultivated meat – chicken from Good Meat – is currently only sold to consumers in Singapore, but two companies have now passed an approval process in the US. In 2018, another company used DNA from an extinct animal to create gummy bears made from gelatine from a mastodon, another elephant-like animal.

Vow worked with Prof Ernst Wolvetang, at the Australian Institute for Bioengineering at the University of Queensland, to create the mammoth muscle protein. His team took the DNA sequence for mammoth myoglobin, a key muscle protein in giving meat its flavor, and filled in the few gaps using elephant DNA. This sequence was placed in myoblast stem cells from a sheep, which replicated to grow to the 20bn cells subsequently used by the company to grow the mammoth meat. “It was ridiculously easy and fast,” said Wolvetang. “We did this in a couple of weeks. Initially, the idea was to produce dodo meat, he said, but the DNA sequences needed do notvyet exist!"

Precision-controlled CAR-T-cell immunotherapies could be used to tackle a range of tumor types.

Elaborately engineered immune cells can not only recognize cancer cells, but also evade defenses that tumors use to fend off attacks, researchers have found. Two studies recently published in Science1,2 build on the success of chimeric antigen receptor (CAR)-T cancer therapies, which use genetically altered T cells to seek out tumors and mark them for destruction. These treatments have the potential to lead to long-lasting remission, but are not successful for everyone, and have so far been effective against only a small number of cancers.

To bolster the power of CAR-T therapies, researchers have further engineered the cells to contain switches that allow control over when and where the cells are active. The hacked cells produce a protein that stimulates T cells, to counteract immunosuppressive signals that are often released by tumors. Both studies are a tour de force in T-cell engineering and highlight the direction that researchers want to push CAR-T-cell therapy, says systems immunologist Grégoire Altan-Bonnet at the US National Cancer Institute. “We know a lot of the parts, now it’s being able to put them together and explore,” he says. “If we engineer the system well, we can really put the tumors into checkmate.”

Engineered immune cells

T cells typically patrol the body, looking for foreign proteins displayed on the surface of cells. Such cells could be infected with a virus, for example, or they could be tumor cells that are producing abnormal, cancer-associated proteins. A class of T cells called killer T cells can then destroy the abnormal cells. CAR-T therapies involve genetically engineering T cells from a person with cancer to produce CARs, which are proteins that recognize the proteins displayed by tumor cells. The approach has been approved to treat some leukemias, lymphomas and myelomas. But researchers have been pursuing ways to make the treatments safer and more effective, and to expand their use to other diseases.

Highly mutated cancers respond better to immune therapy

In one of the new studies, Ahmad Khalil, a synthetic biologist at Boston University in Massachusetts, and his colleagues wired a complex system of 11 DNA sequences into CAR T cells. The resulting genetic circuits can be switched on and off using already-approved drugs, which allows researchers to control when and where the hacked T cells are active, as well as their production of a protein called IL-2, which stimulates immune responses. The other group of researchers, led by synthetic biologist Wendell Lim at the University of California, San Francisco, programmed CAR T cells to produce IL-2 only when the engineered T cell encounters a cancer cell. The team found that this IL-2 production was most efficient at fighting tumors in mice with pancreatic cancer when it was activated through a pathway that was separate from the one used to recognize the cancer cell — a detail that could help in shaping future therapies, says Andrea Schietinger, a tumor immunologist at Memorial Sloan Kettering Cancer Center in New York City.

New Research Finds That Viruses May Have “Eyes and Ears” on Us

The newly-found, widespread ability of some viruses to monitor their environment could have implications for antiviral drug development. New research indicates that viruses are using information from their environment to “decide” when to sit tight inside their hosts and when to multiply and burst out, killing the host cell. The work has important implications for antiviral drug development. Led by the University of Maryland Baltimore County (UMBC), the study was recently published in Frontiers in Microbiology. A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to the viral-host interaction,” says Ivan Erill. He is senior author on the new paper and professor of biological sciences at UMBC. Right now, viruses are taking advantage of that ability to their benefit. But he says that in the future, “we could exploit it to their detriment.”

Phages probably picked up DNA-cutting systems from their microbial hosts, and may use them to fight other viruses. A systematic sweep of viral genomes has revealed a trove of potential CRISPR-based genome-editing tools.

CRISPR–Cas systems are common in the microbial world of bacteria and archaea, where they often help cells to fend off viruses. But an analysis1 published on 23 November 2022 in Cell finds CRISPR–Cas systems in 0.4% of publicly available genome sequences from viruses that can infect these microbes.

Researchers think that the viruses use CRISPR–Cas to compete with one another — and potentially also to manipulate gene activity in their host to their advantage. Some of these viral systems were capable of editing plant and mammalian genomes, and possess features — such as a compact structure and efficient editing — that could make them useful in the laboratory.

“This is a significant step forward in the discovery of the enormous diversity of CRISPR–Cas systems,” says computational biologist Kira Makarova at the US National Center for Biotechnology Information in Bethesda, Maryland. “There is a lot of novelty discovered here.”

DNA-cutting defenses

Although best known as a tool used to alter genomes in the laboratory, CRISPR–Cas can function in nature as a rudimentary immune system. About 40% of sampled bacteria and 85% of sampled archaea have CRISPR–Cas systems. Often, these microbes can capture pieces of an invading virus’s genome, and store the sequences in a region of their own genome, called a CRISPR array. CRISPR arrays then serve as templates to generate RNAs that direct CRISPR-associated (Cas) enzymes to cut the corresponding DNA. This can allow microbes carrying the array to slice up the viral genome and potentially stop viral infections. Viruses sometimes pick up snippets of their hosts’ genomes, and researchers had previously found isolated examples of CRISPR–Cas in viral genomes. If those stolen bits of DNA give the virus a competitive advantage, they could be retained and gradually modified to better serve the viral lifestyle. For example, a virus that infects the bacterium Vibrio cholera uses CRISPR–Cas to slice up and disable DNA in the bacterium that encodes antiviral defences2.

Molecular biologist Jennifer Doudna and microbiologist Jillian Banfield at the University of California, Berkeley, and their colleagues decided to do a more comprehensive search for CRISPR–Cas systems in viruses that infect bacteria and archaea, known as phages. To their surprise, they found about 6,000 of them, including representatives of every known type of CRISPR–Cas system. “Evidence would suggest that these are systems that are useful to phages,” says Doudna. The team found a wide range of variations on the usual CRISPR–Cas structure, with some systems missing components and others unusually compact. “Even if phage-encoded CRISPR–Cas systems are rare, they are highly diverse and widely distributed,” says Anne Chevallereau, who studies phage ecology and evolution at the French National Centre for Scientific Research in Paris. “Nature is full of surprises.”

Small, but efficient

Viral genomes tend to be compact, and some of the viral Cas enzymes were remarkably small. This could offer a particular advantage for genome-editing applications, because smaller enzymes are easier to shuttle into cells. Doudna and her colleagues focused on a particular cluster of small Cas enzymes called Casλ, and found that some of them could be used to edit the genomes of lab-grown cells from thale cress (Arabidopsis thaliana), wheat, as well as human kidney cells. The results suggest that viral Cas enzymes could join a growing collection of gene-editing tools discovered in microbes.

Although researchers have uncovered other small Cas enzymes in nature, many of those have so far been relatively inefficient for genome-editing applications, says Doudna. By contrast, some of the viral Casλ enzymes combine both small size and high efficiency. In the meantime, researchers will continue to search microbes for potential improvements to known CRISPR–Cas systems.

Makarova anticipates that scientists will also be looking for CRISPR–Cas systems that have been picked up by plasmids — bits of DNA that can be transferred from microbe to microbe. “Each year we have thousands of new genomes becoming available, and some of them are from very distinct environments,” she says. “So it’s really going to be interesting.”

Published in Nature (Nov. 23, 2022): https://doi.org/10.1038/d41586-022-03837-8

The development of cancer neoantigen vaccines that prime the anti-tumor immune responses has been hindered in part by challenges in delivery of neoantigens to the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We conjugated attenuated IAVs with the innate immunostimulatory agent CpG and, after intranasal administration to the mouse lung, observed increased immune cell infiltration to the tumor.

OVA was then covalently displayed on IAV-CPG using click chemistry. Vaccination with this construct yielded robust antigen uptake by dendritic cells, a specific immune cell response and a significant increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly, we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced regression of lung metastases and prolonged mouse survival after rechallenge. Engineered IAVs can be equipped with any tumor neoantigen of interest to generate lung cancer vaccines. A cancer vaccine is delivered to the lung by an engineered attenuated influenza virus.

Published in Nature Biotechnology:

https://doi.org/10.1038/s41587-023-01796-7 

Gene therapies have made spectacular progress in delivering new cures for previously intractable disease, but they remain the world’s most expensive treatments by far. Now companies are replacing the virus in gene therapies with new delivery technologies that promise not only to overcome the limitations of viral vectors but to slash production costs too. Moderna and Generation Bio teamed up recently to develop non-viral gene therapies for liver and immune-related conditions, in a deal that builds on Generation Bio’s lipid nanoparticle (LNP) delivery platform. The collaboration is part of a growing trend to swap virus-driven gene therapeutics for innovative nucleic acid delivery platforms that escape the high costs and technical limitations of viral vectors.

Engineered lipid or protein nanobodies, DNA-based nanocarriers, and novel physicochemical methods point the way toward re-dosable genetic medicines (Table 1). Virus-based vectors — particularly those based on adeno-associated virus (AAV) and lentiviruses — have dominated the first wave of gene therapies to gain regulatory approval. But their widespread deployment in dozens of clinical trials has exposed their limitations very clearly. “One of the issues is just the biomass needed to produce a sufficient amount, like AAV at the scale and in the doses needed for large indications,” says Akin Akinc, CEO of Aera Therapeutics, a company developing a protein-nanoparticle-based delivery system. AAV vectors are further limited by their 4.7-kilobase packaging capacity; poor tissue selectivity; risk of liver toxicity; and immunogenicity, which eliminates the possibility of redosing. Lentiviral vectors and, to a lesser extent, AAV vectors also elicit oncogenicity concerns arising from chromosomal integration and insertional mutagenesis. Moreover, the theoretical risk of replication-competent viruses emerging from recombination events during lentiviral production necessitates extensive testing in patients.

A research team led by gene editing pioneer David R. Liu, PhD, reports the application of base editing technology to develop a one-time treatment for spinal muscular atrophy (SMA), showing promising effectiveness in cell and mouse models. Liu, a professor at Harvard University, the Broad Institute, and an investigator with the Howard Hughes Medical Institute, together with 16 co-authors, published their findings today in Science, in a report entitled, “Base editing rescue of spinal muscular atrophy in cells and in mice.”

The paper is the first one published in a peer-reviewed journal that details a base editing approach to treating SMA—the leading genetic cause of infant mortality. Two months ago, Benjamin P. Kleinstiver, PhD, assistant professor in the Center for Genomic Medicine at Massachusetts General Hospital (MGH) and Harvard Medical School, and 12 co-authors posted a related preprint on bioRxiv detailing successful results from their study to optimize and implement a base editing treatment for SMA. In SMA, patients have either a loss of, or mutations in, the SMN1 gene. The result is a lack of its corresponding protein SMN, which is critical to cellular functions that include those required for embryo development. Liu and co-authors detailed how they restored SMN protein abundance to normal levels and rescued disease phenotypes in cell and mouse models of SMA by developing one-time genome editing approaches targeting another gene, called SMN2.

SMN2 differs from SMN1 at just one position—a single C-to-T mutation in exon 7. The result is a defective truncated SMN protein that fails to fully compensate for the loss of SMN1, but which provides just enough SMN protein activity to allow babies to be born with SMA. In the most common SMA cases (type 1), those babies typically live less than two years without treatment. Liu and colleagues developed a customized base editor (out of more than 40 tested) that directly converts SMN2 to the same sequence as SMN1 by reversing the C-to-T mutation that occurred during the duplication of SMN1 to SMN2.

The investigators reported that their strategy converted SMN2 to SMN1 with near-ideal editing efficiency of 99% in cells, fully restoring SMN protein levels ~40-fold to normal levels, while generating minimal off-target edits. “Because all SMA patients have SMN2—otherwise loss of SMN1 would not allow them to be born—this base editing approach to treating SMA also should be applicable to all SMA patients, regardless of the specific mutation that caused their SMN1 loss,” Liu said.

Mitochondria are critical organelles that form networks within our cells, generate energy dynamically, contribute to diverse cell and organ function, and produce a variety of critical signaling molecules, such as cortisol. This intracellular microbiome can differ between cells, tissues, and organs. Mitochondria can change with disease, age, and in response to the environment. Single nucleotide variants in the circular genomes of human mitochondrial DNA are associated with many different life-threatening diseases. Mitochondrial DNA base editing tools have established novel disease models and represent a new possibility toward personalized gene therapies for the treatment of mtDNA-based disorders.

Using new machine learning techniques, researchers at UC San Francisco (UCSF), in collaboration with a team at IBM Research, have developed a virtual molecular library of thousands of "command sentences" for cells, based on combinations of "words" that guided engineered immune cells to seek out and tirelessly kill cancer cells.

The work, published online Dec. 8, 2022, in Science, represents the first time such sophisticated computational approaches have been applied to a field that, until now, has progressed largely through ad hoc tinkering and engineering cells with existing, rather than synthesized, molecules.vThe advance allows scientists to predict which elements – natural or synthesized – they should include in a cell to give it the precise behaviors required to respond effectively to complex diseases. "This is a vital shift for the field," said Wendell Lim, PhD, the Byers Distinguished Professor of Cellular and Molecular Pharmacology, who directs the UCSF Cell Design Institute and led the study. "Only by having that power of prediction can we get to a place where we can rapidly design new cellular therapies that carry out the desired activities."

Meet the molecular words that make cellular command sentences

Much of therapeutic cell engineering involves choosing or creating receptors that, when added to the cell, will enable it to carry out a new function. Receptors are molecules that bridge the cell membrane to sense the outside environment and provide the cell with instructions on how to respond to environmental conditions. Putting the right receptor into a type of immune cell called a T cell can reprogram it to recognize and kill cancer cells. These so-called chimeric antigen receptors (CARs) have been effective against some cancers but not others.

Lim and lead author Kyle Daniels, PhD, a researcher in Lim's lab, focused on the part of a receptor located inside the cell, containing strings of amino acids, referred to as motifs. Each motif acts as a command "word," directing an action inside the cell. How these words are strung together into a "sentence" determines what commands the cell will execute.

A new discovery in the fight against COVID-19 could lead to a long-lasting vaccine that works on all currently known variants of the ever-mutating virus. With new COVID variants and subvariants evolving faster and faster, each chipping away at the effectiveness of the leading vaccines, the hunt is on for a new kind of vaccine — one that works equally well on current and future forms of a novel coronavirus.

Recently, researchers at the National Institutes of Health (NIH) in Maryland think they have found a new approach to vaccine design that could lead them to a long-lasting jab. As an added bonus, it also might also work on other coronaviruses, not just the SARS-CoV-2 virus that causes COVID-19.

The NIH team reported its findings in a peer-reviewed study that appeared in the journal Cell Host & Microbe earlier this month. The key to the NIH’s potential vaccine design is a part of the virus called the “spine helix.” It’s a coil-shaped structure inside the spike protein, the part of the virus that helps it grab onto and infect host cells. Lots of current vaccines target the spike protein. But none of them specifically target the spine helix. And yet, there are good reasons to focus on that part of the pathogen.

Whereas many regions of the spike protein tend to change a lot as the virus mutates, the spine helix doesn’t. That gives scientists “hope that an antibody targeting this region will be more durable and broadly effective,” Joshua Tan, the lead scientist on the NIH team, told The Daily Beast. Vaccines that target and “bind,” say, the receptor-binding domain region of the spike protein might lose effectiveness if the virus evolves within that region. The great thing about the spine helix, from an immunological standpoint, is that it doesn’t mutate. At least, it hasn’t mutated yet, three years into the COVID pandemic. So a vaccine that binds the spine helix in SARS-CoV-2 should hold up for a long time. And it should also work on all the other coronaviruses that also include the spine helix—and there are dozens of them, including several such as SARS-CoV-1 and MERS that have already made the leap from animal populations and caused outbreaks in people.

To test their hypothesis, the NIH researchers extracted antibodies from 19 recovering COVID patients and tested them on samples of five different coronaviruses, including SARS-CoV-2, SARS-CoV-1 and MERS. Of the 55 different antibodies, most zeroed in on parts of the virus that tend to mutate a lot. Just 11 targeted the spine helix. But those 11 that went after the spine helix worked better, on average, on four of the coronaviruses. A fifth virus, HCoV-NL63, shrugged off all the antibodies.

The NIH team isolated the best spine-helix antibody, COV89-22, and also tested it on hamsters infected with the latest subvariants of the Omicron variant of COVID. “Hamsters treated with COV89-22 showed a reduced pathology score,” the team found. The results are promising. “These findings identify a class of antibodies that broadly neutralize coronaviruses by targeting the stem helix,” the researchers wrote. Don’t break out the champagne quite yet.

“Although these data are useful for vaccine design, we have not performed vaccination experiments in this study and thus cannot draw any definitive conclusions with regard to the efficacy of stem helix-based vaccines,” the NIH team warned. It’s one thing to test a few antibodies on hamsters. It’s another to develop, run trials with and get approval for a whole new class of vaccine. “It is really hard and most things that start out as good ideas fail for one reason or another,” James Lawler, an infectious disease expert at the University of Nebraska Medical Center, told The Daily Beast. And while the spine-helix antibodies appear to be broadly effective, it’s unclear how they stack up against antibodies that are more specific. In other words, a spine-helix jab might work against a bunch of different but related viruses, but work less well against any one virus than a jab that’s tailored specifically for that virus. “Further experiments need to be done to evaluate if they will be sufficiently protective in humans,” Tan said of the spine-helix antibodies.

There’s a lot of work to do before a spine-helix vaccine might be available at the corner pharmacy. And there are a lot of things that could derail that work. Additional studies could contradict the NIH team’s results. The new vaccine design might not work as well on people as it does on hamsters. The new jab could also turn out to be unsafe, impractical to produce or too expensive for widespread distribution. Barton Haynes, a Duke University immunologist, told The Daily Beast he looked at spine-helix vaccine designs last year and concluded they’d be too costly to warrant major investment. The main problem, he said, is that the spine-helix antibodies are less potent and “tough to induce” from their parent B-cells. The harder the pharmaceutical industry has to work to produce a vaccine, and the more vaccine it has to pack into a single dose in order to compensate for lower potency, the less cost-effective a vaccine becomes for mass-production. Maybe a spine-helix jab is in our future. Or maybe not.

Either way, it’s encouraging that scientists are making incremental progress toward a more universal coronavirus vaccine. One that could work for many years on a wide array of related viruses. COVID for one isn’t going anywhere. And with each mutation, it risks becoming unrecognizable to the current vaccines. What we need is a vaccine that’s mutation-proof.

Publication cited published in Cell Host and Microbe (Nov. 7, 2022):

https://doi.org/10.1016/j.chom.2022.10.010