Dr. Philp McMillan, John McMillan
The world’s epidemiologists are staring at the wrong part of the virus.
For four and a half years, the scientific community has tracked every mutation on SARS-CoV-2’s spike protein. This protein is the virus’s key to human cells, and it’s been the focus of vaccine development, variant surveillance, and nearly every conversation about viral evolution. When BA.2.86 emerged, scientists sequenced its spike. When XBB.1.5 dominated, they mapped its spike changes. Booster shots get updated to match spike mutations.
Geert Vanden Bossche thinks this focus has blinded us to a more dangerous transformation happening inside the virus.
Vanden Bossche’s resume includes stints at GSK, Novartis, the Bill & Melinda Gates Foundation, and Gavi, where he managed Ebola vaccine deployment during the 2014 crisis. His recent paper describes what he believes is the endgame: a variant that could bypass the adaptive immune system entirely.
He calls it Hivicron.
The Invisible Battlefield
Every virus that infects a cell hijacks the cellular machinery to make copies of itself and leaves traces of its presence. The spike protein sits on the virus’s exterior, making it an obvious target for antibodies. But inside each viral particle sits the nucleocapsid protein, wrapped around the genetic material. This internal scaffolding doesn’t usually change much across variants. It’s structurally conserved, stable, forgettable.
Or it was.
While antibodies patrol the bloodstream looking for intact viruses, T-cells hunt infected cells by recognizing viral protein fragments displayed on their surface. These fragments can come from any part of the virus, including internal proteins like nucleocapsid. When T-cells spot these danger signals, they coordinate a response.
The problem: genomic surveillance focuses overwhelmingly on spike. The CDC’s variant tracking, the WHO’s classification system, even research into immune escape mechanisms center on how spike changes affect antibody binding.
“We are completely missing what’s going on,” Vanden Bossche argues, because the critical mutations are accumulating in nucleocapsid. They’re accumulating in the T-cell epitopes that determine how effectively the immune system can recognize and respond to infection.
If he’s right, we’re tracking the wrong battlefield entirely.
The Evolution of Pressure
Before Omicron emerged in December 2021, the virus evolved primarily to escape neutralizing antibodies. Each new variant carried mutations that made antibodies less effective.
Omicron represented a quantum leap. It caused breakthrough infections in vaccinated populations, triggering a broader immune response. The immune system suddenly produced antibodies against a wider range of viral targets, and T-cell responses expanded. Public health officials celebrated this as robust, cross-protective immunity.
Vanden Bossche saw something else: the beginning of population-level T-cell pressure.
In highly vaccinated populations, most people now rely primarily on T-cell immunity to control the virus. Antibodies no longer neutralize effectively because the virus has evolved past them. What remains is a T-cell response that creates chronic, low-grade infections. Studies from the UK’s Office for National Statistics show Long COVID prevalence continuing to rise in 2024, affecting 1.9 million people as of mid-year. These infections produce high viral loads and ongoing inflammation, but they don’t eliminate the virus.
The immune response is strong enough to be “annoying” to the virus, but not strong enough to stop transmission.
This creates an evolutionary crucible. Variants with mutations in their nucleocapsid T-cell epitopes gain a competitive advantage. They transmit more easily because they partially evade T-cell surveillance. And as more people develop chronic infections, more T-cells get activated, ratcheting up the pressure higher.
The evidence shows up in variant tracking data. The CDC’s Nowcast estimates reveal something striking: new subvariants are achieving dominance faster than before. What once took six months now takes four. The intervals keep shrinking.
Everyone assumes this acceleration reflects minor tweaks to spike infectivity.
Vanden Bossche sees the signature of rapid selection for nucleocapsid mutations that the surveillance system isn’t measuring.
The Endgame Hypothesis
Every evolutionary pressure has limits. What happens when a variant accumulates the maximum possible changes to its T-cell epitopes and still faces mounting immune pressure from chronically infected individuals?
Vanden Bossche’s answer: the virus will take the same kind of leap it took with Omicron, but in a different direction.
Instead of further mutating its T-cell epitopes, it will evolve to bypass T-cell recognition altogether. The mechanism he proposes involves structural changes to the virus’s surface, possibly the addition of sugar molecules called glycans that shield viral proteins from immune detection. This wouldn’t be about specific epitopes anymore. It would be “non-antigen-specific” escape: a fundamental change in how the virus presents itself. Antigen-presenting cells, which normally capture viral fragments and show them to T-cells, would no longer recognize the virus as a threat.
The entire adaptive immune system would be rendered irrelevant.
The clinical implications depend on innate immunity: the body’s first-line, non-specific defenses. In unvaccinated individuals who encountered the virus naturally, repeated exposures trained the innate immune system to respond quickly. These people would face a virus that has become intrinsically less infectious (the “price” it paid for its immune-evasion shield), and their trained innate immunity would likely control it.
But in vaccinated individuals whose breakthrough infections came too fast for innate training, the situation would be different. With no adaptive immunity to fall back on and no trained innate response, the virus would replicate unchecked. In a September 2024 interview, Vanden Bossche described what he envisions: “I’m talking about a hyperacute phase of the pandemic, a hyperacute course of individual disease. The number of casualties will be incredibly higher than we would have seen if we would not have had the mass vaccination.”
This isn’t a slow decline. A 2023 case study in Clinical Infectious Diseases documented an immunosuppressed patient who died of respiratory failure 14 months after initial infection, his body producing cryptic variants that never achieved transmission. That’s intra-host evolution in a single individual.
Hivicron would be different.
It would be a variant selected at the population level because its mutations are in conserved, shared epitopes. When a mutation helps transmission across millions of hosts, it spreads fast. “It will go fast because we are always talking about collective, population-level immune pressure on the virus,” Vanden Bossche explains. He points to Omicron as precedent: a variant that swept the globe within weeks, achieving 95% dominance in many countries by January 2022.
“This time, it will even be much faster.”
The Logic Chain
Mass vaccination created a shared immune landscape across populations. That shared immunity, focused initially on spike-directed antibodies, drove the virus toward Omicron-style immune escape. Omicron’s breakthrough infections shifted the defense to T-cells, which are now under intense pressure. Variants with nucleocapsid mutations are being selected faster and faster. When that evolutionary pathway exhausts itself, the virus will need a new trick.
The surveillance data showing accelerating variant turnover is real. The rise in chronic inflammatory disease and Long COVID in highly vaccinated countries is documented. Australia reported 5% population prevalence as of August 2024. What remains theoretical is the final leap: whether the virus will actually evolve to bypass antigen presentation, and whether the clinical outcome will match Vanden Bossche’s predictions.
The most unsettling aspect of his analysis isn’t the dire forecast.
It’s the suggestion that the current monitoring infrastructure is blind to the signals that would confirm or refute his hypothesis.
If nucleocapsid sequences aren’t being tracked systematically, and if T-cell epitope evolution is attributed to minor spike changes, then the data needed to validate or challenge his reasoning doesn’t exist in usable form. Researchers looking at the CDC’s variant proportion graphs see normal evolutionary drift. Vanden Bossche sees a countdown clock measuring T-cell epitope exhaustion.
He acknowledges the complexity: “Biology is not black and white.” Individual outcomes would vary based on vaccination timing, prior infection status, the severity of breakthrough infections, and underlying health. But the population-level pattern he describes follows a cold logic. A virus under sustained immune pressure will adapt. A population maintaining chronic infections will continue to apply that pressure.
The trajectory doesn’t stop until something fundamental changes.
Whether that change comes as Hivicron (or whether the immune-virus equilibrium finds some other resolution) remains to be seen. What’s certain is that Vanden Bossche has articulated a version of the pandemic’s future that doesn’t end with endemic stability. It ends with one final, acute reckoning between the virus and the adaptive immune system that’s been pursuing it for nearly five years.
The Trojan horse of his analysis is hidden evolution in the nucleocapsid. The elephant in the room is the possibility that by watching spike, we’re missing the story that matters.
What You Can Watch For
If Vanden Bossche’s hypothesis has merit, certain signals should emerge before Hivicron arrives. Long COVID prevalence should continue rising in highly vaccinated populations. Variant turnover should keep accelerating, with new dominant strains emerging in progressively shorter intervals. And if researchers begin sequencing nucleocapsid systematically, they should find accumulating mutations in conserved T-cell epitopes.
More immediately: know your own immune history. Did you have COVID before vaccination? How many breakthrough infections have you had? The answers may matter more than anyone currently realizes.
The data to test his theory exists. It’s just not being collected in the right places yet.
Many thanks for this Timely information and Analysis Dr McMillan
much appreciated and thanks for your continuing Research 🙏