Scientists have made a groundbreaking discovery that could revolutionize the fight against COVID-19. Researchers have found a unique class of antibodies, generated by llamas, that are highly effective against a wide range of SARS coronaviruses, including the one behind COVID-19 and its future variants.

These llama-derived antibodies target an essential region at the base of the virus’s spike protein, effectively shutting it down and preventing the virus from infecting cells. The findings, published in Nature Communications, offer a promising route to developing broad-spectrum antiviral treatments that could remain effective against future viral variants.

The current SARS-CoV-2 vaccine is designed to target specific regions of the virus’s spike protein, which can mutate quickly, leading to resistance. However, the new llama antibodies focus on a more stable subunit of the spike protein, making them harder for the virus to evade.

A team led by Prof. Xavier Saelens and Dr. Bert Schepens at the VIB-UGent Center for Medical Biotechnology discovered that these llama antibodies act like a molecular clamp, locking the spike protein in its original shape and preventing it from unfolding into the form needed to infect cells. The researchers tested the antibodies in lab animals and found strong protection against infection, even at low doses.

Furthermore, when they attempted to force the virus to evolve resistance, it struggled, producing only rare escape variants that were much less infectious. This points to a powerful treatment option that could be hard for the virus to evade.

“This region is so crucial to the virus that it can’t easily mutate without weakening the virus itself,” explains Schepens, senior author of the study. “That gives us a rare advantage: a target that’s both essential and stable across variants.”

This discovery marks a significant advancement in the quest for durable and broadly effective antiviral therapies, offering hope for treatments that can keep pace with viral evolution.

“The combination of high potency, broad activity against numerous viral variants, and a high barrier to resistance is incredibly promising,” adds Saelens. “This work provides a strong foundation for developing next-generation antibodies that could be vital in combating not only current but also future coronavirus threats.”

A team of researchers from the University of Pittsburgh School of Public Health and Pennsylvania State University has made a groundbreaking discovery in the field of vaccine development. They have created a new type of mRNA vaccine that is not only more effective but also less costly to develop, making it a game-changer in the fight against infectious diseases.

The current mRNA vaccines, such as those used to prevent COVID-19, have two significant challenges: they require a high amount of mRNA to produce and are constantly evolving due to the changing nature of viruses like SARS-CoV-2 and H5N1. The researchers addressed these challenges by creating a proof-of-concept COVID-19 vaccine using what’s known as a “trans-amplifying” mRNA platform.

In this approach, the mRNA is separated into two fragments: the antigen sequence and the replicase sequence. The latter can be produced in advance, saving crucial time in the event of a new vaccine needing to be developed urgently and produced at scale. Additionally, the researchers analyzed the spike-protein sequences of all known variants of SARS-CoV-2 for commonalities, rendering what’s known as a “consensus spike protein” as the basis for the vaccine’s antigen.

The results are promising: in mice, the vaccine induced a robust immune response against many strains of SARS-CoV-2. This has the potential for more lasting immunity that would not require updating, because the vaccine has the potential to provide broad protection. Additionally, this format requires an mRNA dose 40 times less than conventional vaccines, so this new approach significantly reduces the overall cost of the vaccine.

The lessons learned from this study could inform more efficient vaccine development for other constantly evolving RNA viruses with pandemic potential, such as bird flu. The researchers hope to apply the principles of this lower-cost, broad-protection antigen design to pressing challenges like bird flu, making it a crucial step in preparing for future pandemics.

The groundbreaking research from the University of Cincinnati has made it possible for specially engineered bacteria to operate as a delivery system for antiviral therapies and vaccines. Led by Nalinikanth Kotagiri, PhD, this innovative approach demonstrates how orally ingested probiotic bacteria can ferry therapeutic agents or vaccine antigens directly to the gut, where viruses typically enter.

The research focuses on the COVID-19 virus, SARS-CoV-2, as a proof-of-concept study. To develop the vaccine version, the team displayed viral proteins on the bacterial surface and harnessed outer-membrane vesicles (OMVs) – nano-sized spheres that bacteria naturally shed – to act as self-propelled delivery vehicles. Once released, OMVs traffic through the gut epithelium, enter blood circulation, and distribute their payload to distant tissues.

Nitin S. Kamble, PhD, a research scientist in Kotagiri’s lab, systematically screened anchor motifs and expression cassettes to optimize antigen density on the probiotic surface. For the vaccine version, the bacteria was designed to express the spike protein found on the surface of the virus that causes COVID-19.

In preclinical animal studies, a two-dose oral regimen generated blood-borne (systemic) antibody levels comparable to intramuscular mRNA vaccination. Notably, it produced markedly higher levels of secretory immunoglobulin A (IgA) in the gut and airways – the antibodies that underlie mucosal immunity, considered critical for blocking infection at the point of entry.

While vaccines are delivered before a person is infected with a virus, antiviral therapies such as monoclonal antibodies are given as a treatment after infection. The team developed another version of engineered E.coli Nissle 1917 to display therapeutic proteins on the surface. To create a post-exposure therapy, the team encoded anti-spike nanobodies: antibodies that are one-tenth the size of conventional monoclonal antibodies.

Although full viral-challenge studies are pending, nanobodies released from the engineered bacteria reached the bloodstream and accumulated in lung tissue, where they neutralized SARS-CoV-2 in ex-vivo assays. This innovative approach has the potential to revolutionize the field of antiviral therapies and vaccines, offering a novel delivery system that targets the mucosal surfaces in the gut and airways.

The next steps involve validating the safety and efficacy of this delivery system for new engineered bacteria targeting other viruses. Clinical trials will be essential to confirm the effectiveness of this approach, but the initial results are promising. If successful, this technology could lead to a significant advancement in the prevention and treatment of viral infections, offering a more effective and convenient way to deliver vaccines and therapies.