Protection, Interrupted: How Chasing Sterilizing Immunity Fails the Herd

Summary

In the early days of infectious disease science, scientists observed some people not getting

sick and assumed they had immunity so strong, it stopped the germs before they could infect even a single cell. That assumption became known as sterilizing immunity—and it’s been held up as the gold standard ever since. But what if that standard is not only unrealistic, but unmeasurable?

In this episode of Infectious Dose, Heather unpacks the seductive myth of sterilizing immunity and the damage it’s done to public trust, vaccine policy, and our understanding of what vaccine success really looks like. From the 19th-century measles epidemic that birthed the concept, to the modern confusion over COVID-19 "breakthrough infections," we trace how science, history, and public messaging collided in ways that still shape vaccine debates.

We’ll also look at how this fallacy impacts herd immunity, what eradication campaigns like smallpox and polio can teach us, and why aiming for this unachievable ideal has distracted us from the most important goal: public protection.

Listen here or scroll down to read full episode.

Full Episode

During the COVID-19 vaccine rollout, millions of people asked the same question:

“If I got vaccinated, why did I still get infected?”

For many, the answer was clear, but wrong:

“The vaccine didn’t work.”

That reaction wasn’t just a misunderstanding. It was the result of how we talked about vaccines, what we promised, and what the public came to expect.

Today on Infectious Dose, we’re unpacking one of the most persistent myths in immunology; a concept that’s as scientifically seductive as it is misunderstood: sterilizing immunity—the idea that a vaccine must block infection entirely to be considered successful. We’ll explore how this ideal took root, how it’s shaped our expectations of vaccines like those for COVID-19, HPV, and measles—and why this misunderstanding continues to undermine public trust, vaccine uptake, and our ability to achieve herd immunity.

Because it's about more than immunology. It’s about expectations, trust, and how we talk about vaccines in ways that either help or hinder public health.

This is Protection, Interrupted: How Chasing Sterilizing Immunity Fails the Herd.

OK, so I argued about sterilizing immunity back in the early days of COVID and when Katherine Wu published her story in the Atlantic in 2021, I was thrilled. Finally, someone got it! And like her in her Atlantic story, I begin in some cold rocky islands north of Scotland, because to understand the issue, it's really where you have to begin. I could contrive somewhere else to start and end up back here or just start here and give my apologies to Katherine.

Either way, we have to go back. Way back. To where Dr. Peter Panum went in search of measles.

The Measles Misreading

Dr. Panum was a Danish physician who traveled to the Faroe Islands in 1846 to study a measles outbreak. What he discovered became foundational to immunological thinking: people who had lived through a measles epidemic 65 years before weren’t getting sick again.

“Not one,” Panum wrote, “was attacked the second time.”

PanumMeasles.pdf

Download PDF • 1.71MB

This observation, made before viruses, antibodies, or T cells were even discovered, helped seed the idea of lifelong, perfect immunity; the kind that acts like a locked door, barring the pathogen from reentry. Immunity that not only prevents illness, but prevents infection entirely. No pathogen entry. No replication. No transmission. Not even one infected cell.

This is what people now call sterilizing immunity. I call it an unmeasurable overstatement.

And measles, with its extraordinarily effective vaccine, is still held up as a textbook example of sterilizing immunity. The HPV vaccine is another often touted as providing this kind of immunity.

But the story isn’t quite so simple.

Those elder islanders could very well have been infected by measles in 1846. It's possible their immune systems, primed decades earlier, intercepted and shut down the virus before symptoms appeared. No fever. No rash. The thing is, whether they were infected at all or not is not something we can know or prove.

I argue it's more plausible that they were infected and the immune response shut it down, than that they had not even one cell infected. We have recovered live measles virus from people who had been vaccinated and got infected, some with no symptoms and some with mild disease. It freaks people out because they all have this idea, because of Peter Panum, that measles infection or vaccination results in sterilizing immunity. That early assumption haunts us.

And I don't understand that. Those elders didn't get sick. Who cares if they got infected? If their pre-existing immunity protected them from illness then yay!

But the myth of a perfect vaccine persists. It’s a misunderstanding that started with Panum and leads us to ask too much of vaccines, while understanding too little of what they’re truly designed to do.

The Appeal of Sterilizing Immunity—and Why It’s Misleading

The thing is, at first glance, sterilizing immunity sounds like the holy grail. If no one gets infected, no one can transmit. In theory, you could eradicate a virus entirely. So it’s tempting to say: “That’s what we should aim for with every vaccine.”

And, some vaccines—like those for measles or HPV—appear to come close to inducing sterilizing immunity.

And this is where we run into problems.

First—you can’t measure it. Not really.

To prove sterilizing immunity in a living human, you’d need to show that no cells were infected at all, ever. And the reason I say that, is because that's the argument I've been presented with by other virologists: that not even one cell was infected, with for example, the HPV vaccine. So I'm addressing that argument. But you cannot show that no cells were infected at all, ever. That’s not something you can ethically or technically do. You’d need real-time tissue sampling—maybe from the lungs, mucosal surfaces, lymph nodes—to see whether a virus was ever there or replicated. You can’t do that in practice.

So what's the vaccine doing? Well, for HPV, studies show that the vaccine generates strong systemic and mucosal antibody responses, which is part of why it’s so effective. The vaccine-generated antibodies likely clear the virus before we can detect infection (viral DNA or lesions). That’s excellent. That’s protection. But that’s not the same as proving no infection ever occurred. In fact, the authors note that we can’t currently measure that level of immune exclusion. What we can measure is outcome: no detectable virus, no disease, and no transmission.

Even the developers of the HPV vaccine, admit this uncertainty. In The Atlantic story, Katherine Wu quotes vaccinologist Bryce Chackerian saying, “Have we absolutely shown sterilizing immunity? We haven’t.”

And that’s the point: sterilizing immunity isn’t measurable.

Same thing with measles. We know the vaccine works incredibly well, and outbreaks among vaccinated individuals are exceedingly rare. But we don’t sample airway cells to prove that not even one virus particle made contact.

So we’re basing this gold standard on a measurement we can’t actually confirm.

So the HPV and measles vaccines do exactly what a good vaccine should do. But holding them up as proof of sterilizing immunity misses the point, and sets unrealistic expectations for vaccines against more complex, rapidly mutating viruses like SARS-CoV-2 that replicate rapidly, mutate quickly, and have developed ways to evade early immune detection.

Even the best vaccines for these viruses would never achieve sterilizing immunity, even if it was a real thing, not because we’re failing as scientists, but because the biology doesn’t allow it.

So why are we still trying to measure success against this impossible ideal?

What Vaccines Actually Do—And Why That’s Enough

OK, so let's talk about what vaccines actually do; what we should expect them to do. First let's clarify a couple of things: infection is a pathogen getting in. Productive infection is a pathogen getting in, setting up shop, and spreading its seed, so to say. I would concede that immunity from vaccines can prevent productive infection, but not initial infection. Even with HPV, when the virus could encounter immune components in the mucosa before entering a cell, but where, I would also argue, microabrasions from sex compromise the mucosal epithelial barrier allowing, you guessed it, infection. Am I arguing over semantics? No. It's a distinction that needs to be made. Not being accurate in our messaging around sterilizing immunity has damaged trust in public health and vaccines and significantly hurt our efforts to work towards herd immunity.

So what do vaccines accomplish? Say Hello to my little friend, Protective Immunity.

OK, so in contrast to sterilizing immunity, protective immunity doesn’t stop the pathogen from getting in. It allows for some infection at the cellular level—but it kicks in fast enough to prevent serious disease. Depending on how fast a virus can do it's thing, this protective immunity can either prevent productive infection altogether, or beat back productive infection. You might get a few infected cells. Maybe you even get mild symptoms. But you don’t get hospitalized. You don’t die. Your immune system protects you, even without sterilizing immunity.

In the real world, effective vaccines:

• Train the immune system to recognize threats earlier,

• Reduce viral load and shorten illness duration,

• Lower the risk of severe disease, hospitalization, and death,

• And reduce transmission, even if not perfectly.

Look at COVID-19. Data showed:

• Significant reductions in hospitalizations, ICU admissions, and deaths

• Lower viral loads in vaccinated individuals who still got infected,

• Fewer secondary infections—especially when coverage was high.

• Reduced transmission, even if not perfectly

That’s massive. It’s the difference between a pandemic spiraling out of control—and one that’s manageable. Insisting that vaccines “fail” because they don’t prevent all infections is like saying seatbelts are useless because some people get bruises. We don’t need perfection. We need protection.

However sick you got even though you were vaccinated, you would have been a whole lot sicker without the vaccination. That, you can count on.

Despite the data, we have significant antagonism toward covid vaccines. And that is from the way we talked about vaccines in general but also COVID vaccines in particular. And this is a disaster for community-level protection against outbreaks, epidemics, and future pandemics.

Where Messaging Meets Immunity

A growing body of research confirms what many of us in science communication have long feared: vague or overpromising vaccine messages don’t just confuse people — they make them angry.

One behavioral study found that when herd immunity wasn’t explained, vaccine mandates triggered emotional backlash and even reduced future vaccine intentions. Why? Because without a clear understanding of how partial immunity protects communities, people often interpret imperfect vaccines as failures — and public health policies as overreach.

This is where herd immunity intersects with the myth of sterilizing immunity. Because when we define vaccine success as “no infection at all,” we set ourselves up for disappointment — and we erode trust in the tools that actually do work.

So let’s clarify what herd immunity actually is — and what it isn’t.

What Is Herd Immunity?

Herd immunity — also known as indirect protection — occurs when a large enough proportion of a population becomes immune to a pathogen, either through vaccination or prior infection, such that sustained transmission becomes unlikely. As a result, even people who are not immune, like newborns, immunocompromised individuals, or those undergoing cancer treatment, gain protection because the pathogen can’t spread easily.

It’s essential to understand: herd immunity is not about individual protection. It’s a population-level phenomenon that reshapes the pathogen’s ability to circulate.

At the heart of herd immunity is the basic reproduction number, R₀ — the average number of people an infected person will transmit the disease to in a fully susceptible population. To interrupt sustained spread, the effective reproduction number, Rₑ, must fall below 1.

That’s where the herd immunity threshold (HIT) comes in — the percentage of immune individuals needed to push Rₑ below 1. For measles, with an R₀ of 12 to 18, over 90–95% of the population must be immune to prevent outbreaks. For early strains of SARS-CoV-2, HIT was estimated at 60–70%, but the emergence of more transmissible variants like Delta and Omicron pushed that number much higher.

Key Properties of Herd Immunity:

• Pathogen-specific: Different diseases require different thresholds depending on transmissibility.

• Dynamic: Influenced by seasonality, human behavior, population density, and contact patterns.

• Incomplete: It doesn’t eliminate all infections — it reduces the likelihood of sustained transmission.

Herd Immunity ≠ Sterilizing Immunity

One of the most persistent misconceptions is that herd immunity requires sterilizing immunity — the kind that completely blocks infection at the cellular level.

But that’s simply not true.

Vaccines don’t need to prevent all infections to help reduce spread. In fact, non-sterilizing vaccines — which include essentially every vaccine in use today — can still meaningfully reduce transmission by:

• Lowering viral load

• Shortening the infectious period

• Reducing symptomatic and severe illness

If enough people are vaccinated, even imperfect protection can combine at the population level to disrupt chains of transmission.

This isn’t an abstract concept — it’s the math that determines whether your community can stay safe during an outbreak.

The Fragility of the Herd Effect

A 2020 modeling study published in Vaccines explored this concept — often called the “herd effect.” Researchers found that even partial immunity in a population can significantly slow down transmission and delay epidemic peaks.

But that effect is fragile. It depends on:

• Maintaining high vaccine coverage

• Boosting waning immunity

• Staying ahead of viral evolution

If coverage drops or a new variant escapes existing immunity, the protective buffer herd immunity provides can disappear quickly.

That’s exactly what we’ve seen with SARS-CoV-2 — a virus that spreads asymptomatically, evolves rapidly, and induces immunity that fades over time. A 2022 paper laid this out clearly: for pathogens with those traits, herd immunity is not an achievable finish line. It’s a moving target that must be managed over time — not a milestone we reach and leave behind.

Measles as a Counterexample

But let’s be clear: that’s not true of every virus.

Take measles. It's far more contagious than COVID-19, with an R₀ as high as 18. And yet, we’ve controlled measles outbreaks in many countries for decades. Why? Because the vaccine is extremely effective. The virus doesn’t mutate much. And immunity lasts for decades. The only reason we’re seeing measles outbreaks today? Vaccine coverage is slipping. We’re not losing to the virus, we’re losing to misinformation and erosion of public trust.

Why Messaging Matters So Much

And this is where we return to the consequences of misaligned messaging.

If we tell people that vaccines “don’t work” because they don’t block every infection, we’re not just confusing them, we’re undermining the very logic of herd immunity. That misunderstanding drives down uptake, disrupts campaigns, and fuels the spread of preventable diseases.

A 2025 review of international vaccine research found that even healthcare workers — trusted messengers in vaccination efforts — are not immune to misinformation and shifting narratives. If even clinicians struggle to define what vaccine success looks like, it’s no surprise that the public does too.

Herd immunity isn’t a fantasy. But achieving it today requires us to frame it accurately, communicate it clearly, and pursue it equitably, especially in regions where access, infrastructure, and trust are fragile.

A 2024 study in Clinical Pathology stressed that in low- and middle-income countries, where ICU capacity is limited and vaccines often arrive late (or not at all), herd immunity can mean the difference between containment and collapse.

What prevents us from reaching it? The same recurring culprits:

• Misinformation

• Unequal access

• Uncoordinated messaging

The Myth of “Natural Herd Immunity”

We also can’t talk about herd immunity without addressing one of the most dangerous ideas floated early in the pandemic: the notion that we could “let the virus burn through” the population to build natural immunity.

Virologist Angela Rasmussen, in a 2021 paper titled Vaccination Is the Only Acceptable Path to Herd Immunity, laid out the argument clearly:

• Letting SARS-CoV-2 spread unchecked would result in millions of deaths,

• Countless long-term complications from Long COVID,

• And a healthcare system pushed beyond collapse.

Even then, true herd immunity wouldn’t be guaranteed. Reinfections were already occurring. Immunity from natural infection varied widely. And the idea of safely exposing only “low-risk” groups was never practical. Rasmussen’s conclusion: natural infection is not a strategy. It’s a surrender. Vaccination is the only safe, ethical, and effective path forward.

Where the Narrative Went Wrong

So how did we end up here?

In the early rollout of COVID vaccines, we heard oversimplified messages: “The vaccine stops the virus.” “You won’t get infected.”

The problem? That messaging promised sterilizing immunity — and set us up for disappointment.

When Delta and Omicron emerged, and vaccinated people got infected, many felt betrayed. The public saw goalposts moving — first “you won’t get COVID,” then “you won’t get severely ill.” That reversal, even if based on updated science, looked like dishonesty. It damaged trust.

We should never have used the term “breakthrough infection.” It implies failure. The more honest and accurate message would have been: vaccines don’t stop all infection — they stop serious disease.

Reframing the Future

Here’s the paradox: idealizing sterilizing immunity may actually make it harder to achieve herd immunity.

By setting unrealistic expectations, we discouraged uptake of life-saving vaccines. Some people skipped boosters. Others tuned out entirely.

We traded trust for perfection — and lost both.

What if we had communicated these outcomes instead?

• Reduced hospitalizations

• Fewer ICU admissions

• Lower death rates

• Slower community spread

• Less pressure on healthcare systems

These are measurable. Achievable. And meaningful.

Vaccines aren’t magic shields. They’re evolving tools — tools that save lives even when they don’t prevent every infection.

As we develop next-generation vaccines — mucosal platforms, intranasal delivery, better boosters — we may inch closer to blocking transmission at its source.

But we should never again tie public trust to a biological ideal we can’t measure, can’t guarantee, and likely can’t deliver.

Vaccines should be judged by the lives they save — not the few viral particles they don’t stop.

Because the consequences of chasing sterilizing immunity go beyond public perception — they distort how we think about what’s possible in disease control. When we hinge eradication on an ideal we almost never reach, we risk ignoring the tools that actually work.

So let’s ask the more practical question:

What does it really take to eliminate a virus or bacterium — especially when sterilizing immunity is out of reach?

Based on everything we've explored today, it might seem that without sterilizing immunity — immunity that completely blocks infection — eradication is out of the question. And it’s true that if such immunity existed broadly, eradication would be cleaner, faster, more straightforward.

But let’s be clear: eradication doesn’t require perfect vaccines.

What it does require is a convergence — the right biology, the right strategy, and the political will to act on both.

First, you need very high vaccine coverage. Even a non-sterilizing vaccine can reduce transmission if enough people are immune. It’s a numbers game—lowering the average number of people each infected person passes the disease to. That’s the principle behind herd immunity, and it works even when vaccines only reduce viral load or shorten the infectious period.

Second, we need to recognize that herd immunity isn’t a binary switch. It’s a buffer. Vaccines that don’t completely stop infection can still help delay outbreaks, reduce severity, and lower transmission—especially when immunity is widespread and boosted at regular intervals.

But that only gets us so far.

If a pathogen spreads before symptoms appear, mutates quickly, or lingers in animal reservoirs, eradication becomes much harder.

And that’s where public health strategy comes in. If we can't eliminate animal reservoirs, we can sometimes control them. That means vaccinating or monitoring animals—as we’ve done with rabies in wild canines, and as has been proposed for livestock and even wildlife in some zoonotic outbreaks. These approaches are imperfect, but they’re part of a layered strategy to contain transmission.

Another key piece? Updated vaccines. Pathogens like SARS-CoV-2 evolve. Immunity wanes. And if we want any chance at long-term control—even if not eradication—we need to stay ahead of viral evolution. A really effective complement to current vaccines would be intranasal mucosal vaccines for SARS-CoV-2, not to replace but to bolster. These build immunity at the site of infection, (like HPV vaccines). Instead of just teaching the body to fight the virus once it’s inside, these vaccines could help block the virus right at the entry point.

They work by stimulating mucosal immunity, especially secretory IgA antibodies, which act like local bodyguards in your respiratory and digestive tracts. These vaccines may:

• Reduce viral replication in the nose and throat

• Lower the chances of spreading the virus to others

• Provide a more durable first line of defense

While promising, mucosal COVID vaccines face unique challenges in formulation, delivery, and durability. But if successful, they could complement existing vaccines—not replace them—and play a major role in limiting transmission.

But here in the U.S., that progress may be under threat. RFKjr, has said he would require updated COVID-19 vaccines to jump through the hoops new drugs do rather than just being considered updates. That’s not just scientifically unsound—it’s dangerous. Treating updated COVID vaccines like brand-new drugs would severely slow their rollout, leaving the population vulnerable to immune-evading variants. The virus evolves faster than bureaucracy. Our response has to match that speed—or we lose the upper hand.

So no—eradication without sterilizing immunity isn’t impossible. But it’s only achievable when we:

• Maintain high global vaccination rates

• Implement robust surveillance and outbreak response

  • proactive contact tracing, isolation, and ring vaccination

• Address animal reservoirs where possible

• Update vaccines regularly

• And most of all, ensure that science drives policy—not politics.

Sterilizing immunity would be ideal. But in its absence, we don’t give up. We adapt. We protect. And we keep building toward a world where the next outbreak doesn’t become the next disaster.

Before we close, let’s look at two diseases where imperfect vaccines helped us come close to total eradication: smallpox and polio.

Eradication Without Sterilization – The Smallpox and Polio Lessons

Now, I know what some of you are thinking. If sterilizing immunity isn’t necessary, how did we eradicate smallpox? Or nearly wipe out polio?

Let’s take a closer look.

Smallpox: A Triumph of Functional Immunity and Strategy

The smallpox vaccine—developed from the vaccinia virus—didn’t necessarily prevent all infections at the cellular level. It often caused a localized skin reaction, meaning the immune system had been exposed and activated.

And yet, smallpox was declared eradicated in 1980. So how?

A few key factors:

• No animal reservoir: Smallpox infected only humans.

• Long incubation period: Gave public health teams time to identify cases and ring-vaccinate contacts.

  • Ring vaccination is a targeted vaccination strategy used in outbreak response. When someone is diagnosed with an infectious disease, public health teams identify their close contacts—and sometimes contacts of contacts—and vaccinate those individuals to create a "ring" of immunity around the case. This ring helps contain the spread of the disease by cutting off potential chains of transmission.

    It’s efficient—you don’t need to vaccinate everyone.

    It’s timely—you focus on people most likely to be infected next.

    It works best when paired with rapid contact tracing and case isolation.

• Visible symptoms: Made it easier to detect and isolate infections.

• And yes, a very effective vaccine—not sterilizing, but robust enough to stop disease and limit transmission.

So eradication didn’t require a magical shield. It required coordinated action and a vaccine that worked well enough.

Polio: A Tale of Two Vaccines

Polio is another useful case study. We have two vaccines:

1. Inactivated polio vaccine (IPV): Prevents disease but doesn't fully block gut infection.

2. Oral polio vaccine (OPV): Contains a live attenuated virus that can replicate briefly in the gut and be shed—but it also creates stronger mucosal immunity and helps block fecal transmission.

OPV isn’t sterilizing either. In fact, in rare cases it can revert to a virulent form. Yet, it’s been instrumental in slashing global polio cases by over 99%.

And again—no animal reservoir, strong public health systems, high vaccine coverage. That’s what brought us to the brink of eradication—not perfect immunity at the cellular level.

Takeaway:

Sterilizing immunity wasn’t necessary for smallpox eradication or for nearly eliminating polio. What mattered more was high population immunity, coordinated surveillance, rapid response, and vaccines that protected people and slowed transmission—imperfectly but effectively.

So let's start by changing the messaging. Sterilizing immunity should not be the metric by which vaccine success is judged. Vaccines should be evaluated by the lives they save, not the few virus particles they don’t stop.

Help me spread the word.

If you found this episode useful, share it with a colleague, a friend, or someone still wondering why breakthrough infections aren’t failures.

Remember: science is a process—not a promise. And the more accurately we communicate it, the better chance we have at building public trust, saving lives, and meeting the next pandemic with clarity—not confusion.