The same mRNA technology that brought us COVID-19 vaccines is now paving the way for a universal antiviral that could protect us from unknown future threats.
For a few dozen people in the world, a rare genetic mutation grants an extraordinary superpower: the ability to fight off virtually any virus. While they navigate life with mild, persistent inflammation, their immune systems silently defeat invaders like influenza and measles without them ever feeling ill. This remarkable natural phenomenon has inspired scientists at Columbia University to develop an experimental therapy that could temporarily give us all a similar defense 8 .
This breakthrough represents the next frontier in a centuries-old battle against viral pathogens.
For as long as viruses have threatened human existence, we have sought ways to arm our bodies against them. From the early practice of variolation in ancient China to Edward Jenner's first smallpox vaccine in 1796, the fundamental strategy has remained consistent: safely introduce a recognizable piece of a pathogen to train the immune system for future encounters 4 . Today, biomedical engineering is revolutionizing this approach, creating sophisticated vaccines that work better, safer, and faster than ever before.
COVID-19 vaccines demonstrated the potential of mRNA technology
New approaches aim to protect against multiple viruses simultaneously
Engineering approaches enable faster vaccine development
Vaccines work by mimicking natural infection without causing disease, priming our immune systems to recognize and neutralize specific pathogens. Scientists have developed several engineering approaches to achieve this, each with distinct advantages and applications 9 .
Use weakened forms of viruses that can still replicate but don't cause illness. The measles, mumps, and rubella (MMR) vaccine is a classic example. These vaccines typically provoke strong, long-lasting immunity but aren't suitable for people with compromised immune systems 9 .
Contain viruses that have been "killed" using chemical or physical methods, rendering them non-infectious while preserving their structure. The original polio vaccine developed by Jonas Salk uses this approach. While safer for immunocompromised individuals, these vaccines often require multiple doses and adjuvants 4 9 .
Include only specific, recognizable parts of a virus—like the spike protein of SARS-CoV-2—rather than the entire pathogen. By presenting these key antigens, they teach the immune system to target crucial viral components while minimizing side effects 9 .
Represent the cutting edge of vaccine technology. Instead of injecting viral proteins, these vaccines deliver genetic instructions (DNA or mRNA) that teach our own cells to temporarily produce a viral protein. This method, used in COVID-19 vaccines, combines strong immune response with rapid development and scalability 7 .
| Vaccine Type | Mechanism | Advantages | Limitations | Examples |
|---|---|---|---|---|
| Live Attenuated | Weakened live virus | Strong, long-lasting immunity; often single dose | Not for immunocompromised; potential for reversion | MMR, Chickenpox 9 |
| Inactivated | Killed whole virus | Safer for vulnerable populations | Often requires boosters, adjuvants | Polio (Salk), Rabies 4 9 |
| Subunit/Recombinant | Viral protein fragments | High safety; no live components | May require adjuvants; multiple doses | Hepatitis B, HPV 9 |
| mRNA | Genetic code for viral protein | Rapid development; strong immune response | Cold chain storage; relatively new technology | COVID-19 (Pfizer, Moderna) 7 |
One of the most promising advancements in vaccine engineering involves nanoparticles—vanishingly small particles that serve as molecular delivery vehicles or even as the vaccine structure itself.
Crucial delivery vehicles, particularly for mRNA vaccines. These tiny fat bubbles protect fragile genetic material as it travels through the body and help shepherd it into cells 7 .
Sophisticated structures designed to display specific viral antigens in precise patterns and densities, potentially yielding stronger and broader protection than conventional vaccines 7 .
The quest for broad-spectrum antiviral protection represents one of the most ambitious goals in vaccine engineering. Most vaccines target specific viruses, but what if we could develop a universal protection, even against future pandemic threats?
The journey began when immunologist Dusan Bogunovic and his team studied a rare immune disorder caused by a deficiency in a protein called ISG15. Though affected individuals were more vulnerable to some bacterial infections, they displayed remarkable resistance to viruses 8 .
Further investigation revealed that these individuals had mild, persistent systemic inflammation of a specific "antiviral" type. Bogunovic realized that if he could temporarily recreate this protective state in others, it could provide broad protection against multiple viruses 8 .
Individuals with ISG15 deficiency showed evidence of encounters with various viruses—flu, measles, chickenpox—yet they never reported feeling sick 8 .
Rather than permanently disabling ISG15 (which would cause unwanted side effects), the Columbia team designed a sophisticated temporary workaround. They created an mRNA-based therapeutic that bypasses ISG15 to directly activate the ten proteins primarily responsible for the broad antiviral protection observed in ISG15-deficient individuals 8 .
Researchers packaged ten different mRNA sequences—each encoding one of the ten key antiviral proteins—into lipid nanoparticles similar to those used in COVID-19 vaccines 8 .
The therapeutic was administered to mice and hamsters via nasal drip, targeting the respiratory system where many viruses first enter the body 8 .
Treated animals were exposed to influenza and SARS-CoV-2 viruses 8 .
Researchers tracked viral replication, disease symptoms, and immune responses compared to untreated control animals 8 .
The experimental therapy successfully prevented viral replication of both influenza and SARS-CoV-2 viruses in the treated animals and significantly reduced disease severity. In cell culture experiments, the researchers noted: "We have yet to find a virus that can break through the therapy's defenses" 8 .
| Experimental Measure | Treated Group | Control Group | Significance |
|---|---|---|---|
| Influenza viral replication | Prevented | Normal progression | First evidence of broad-spectrum protection |
| SARS-CoV-2 viral load | Significantly reduced | High viral load | Effective against diverse virus families |
| Disease severity | Lessened | Severe symptoms | Protection against clinical illness |
| Range of efficacy | All viruses tested in cell culture | Variable susceptibility | Potential for true universal protection |
The therapy generated just enough of the ten proteins to create antiviral protection without causing significant inflammation. Critically, this approach doesn't prevent people from developing their own immunological memory to specific viruses for longer-term protection 8 .
The rapid development of COVID-19 vaccines demonstrated how decades of research in vaccine engineering could culminate in a global lifesaving effort. The 2025-2026 COVID-19 vaccines—including updated formulations from Moderna, Pfizer/BioNTech, and Novavax—continue to protect vulnerable populations, particularly those who are immunocompromised 1 5 .
Creating advanced antiviral vaccines requires specialized reagents and tools that allow researchers to design, test, and refine their formulations.
Our findings reinforce the power of research driven by curiosity without preconceived notions. We were not looking for an antiviral when we began studying our rare patients, but the studies have inspired the potential development of a universal antiviral for everyone.8
First Smallpox Vaccine
Inactivated Vaccines
Recombinant Vaccines
mRNA Revolution
From training our immune systems with carefully engineered viral mimics to potentially providing temporary universal protection, science is developing increasingly sophisticated strategies to defend against viral threats—both known and unknown. As these technologies mature, we move closer to a future where pandemics are manageable and preventable, rather than catastrophic.