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COVID and SARS

The Booster Dose Boost: New Research Reveals Why Vaccination Site Matters for Immune Response

Scientists have uncovered why vaccines can elicit a stronger immune response if they are administered in the same arm.

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The recent study conducted by scientists at the Garvan Institute of Medical Research and the Kirby Institute at UNSW Sydney has shed new light on how vaccination site can impact the effectiveness of immune response. The research, published in the journal Cell, found that receiving a booster vaccine in the same arm as your first dose can generate a more effective immune response more quickly.

The study’s findings are based on observations made in mice and validated in human participants. It was discovered that when a vaccine is administered, specialized immune cells called macrophages become “primed” inside lymph nodes. These primed macrophages then direct the positioning of memory B cells to respond more effectively to the booster when given in the same arm.

“This is a fundamental discovery in how the immune system organizes itself to respond better to external threats,” says Professor Tri Phan, Director of the Precision Immunology Program at Garvan and co-senior author. “Nature has come up with this brilliant system, and we’re just now beginning to understand it.”

The researchers used state-of-the-art intravital imaging at Garvan to observe how memory B cells migrate to the outer layer of the local lymph node, where they interact closely with macrophages that reside there. When a booster was given in the same location, these primed macrophages efficiently captured the antigen and activated the memory B cells to make high-quality antibodies.

Dr Rama Dhenni, co-first author of the study, notes, “Macrophages are known to gobble up pathogens and clear away dead cells, but our research suggests that the ones in the lymph nodes closest to the injection site also play a central role in orchestrating an effective vaccine response the next time around. So location does matter.”

A clinical study conducted by the Kirby Institute with 30 volunteers receiving the Pfizer-BioNTech COVID-19 mRNA vaccine validated these findings. Participants who received their booster dose in the same arm as their first dose produced neutralizing antibodies against SARS-CoV-2 significantly faster, within the first week after the second dose.

“These antibodies from the same-arm group were also more effective against variants like Delta and Omicron,” says Dr Mee Ling Munier, co-senior author. “By four weeks, both groups had similar antibody levels, but that early protection could be crucial during an outbreak.”

The study’s findings offer a promising new approach for enhancing vaccine effectiveness, particularly in the context of rapidly mutating viruses where speed of response matters.

“If we can understand how to replicate or enhance the interactions between memory B cells and these macrophages, we may be able to design next-generation vaccines that require fewer boosters,” says Professor Phan.

Cold and Flu

Scientists Discover Llama Antibodies That Shut Down COVID-19 and Its Future Variants

Powerful llama-derived antibodies could be the key to stopping not just current SARS viruses, but future ones too. Scientists have discovered a unique class of nanobodies that clamp the coronavirus spike protein shut at a highly conserved region, rendering it unable to infect cells. Unlike existing therapies that target mutating regions, this approach strikes at the virus s core machinery, giving it little room to evolve. Even when pushed to mutate, the virus faltered, making this a high-potential strategy for broad, lasting protection.

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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.”

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Biochemistry

A Game-Changing mRNA Vaccine that’s More Effective and Less Costly to Develop

A new type of mRNA vaccine is more scalable and adaptable to continuously evolving viruses such as SARS-CoV-2 and H5N1, according to a new study.

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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.

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Bacteria

Engineered Bacteria Deliver Antiviral Therapies and Vaccines with Unprecedented Ease

New research demonstrates how specially engineered bacteria taken orally can operate as a delivery system for vaccines and antiviral therapies.

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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.

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