Connect with us

Why resistance is common in antibiotics, but rare in vaccines

How resistance to drugs originates, and why it’s different for vaccines.

Published

on

Antibiotic resistance is a worldwide problem to the extent that there is a grave risk that common infections will soon become untreatable. Meanwhile, vaccines developed nearly a century ago still protect us from deadly diseases. What might explain this difference?

Bacteria have evolved resistance to every antibiotic ever developed. Sometimes this happened very soon after an antibiotic was first introduced. It took just six years for resistance to penicillin, the first antibiotic, to become widespread in British hospitals.

But resistance against vaccines has only happened rarely. And vaccines have helped us to eradicate smallpox and hopefully soon also polio. A previous study proposed two convincing arguments to explain this phenomenon, by highlighting crucial differences between the mechanisms of drugs and vaccines.

Time from development of an antibiotic/vaccine to first detection of resistance. While resistance has been observed against every single antibiotics, resistance is not a problem for most vaccines.

But first, let’s explain what we mean by resistance and how it originates. During an infection, viruses and bacteria multiply rapidly. In the process, they copy their genetic material millions of times. While doing so, mistakes often happen, with every mistake slightly altering their genomes. These errors are called mutations.

More often than not, mutations have little to no effect or are highly detrimental to the effectiveness of the virus. But sometimes – very rarely – pathogens can get lucky and a mutation can prevent an antibiotic from entering a cell or change the site where a drug or an antibody would bind, stopping them from working. We call these “resistance” or “escape” mutations.

First difference: number of targets

Vaccines work by introducing a harmless part of a pathogen, called an antigen, into the body. They train our immune system to produce Y-shaped proteins, or antibodies, that bind specifically to them. They also stimulate the production of specific white blood cells called T-cells, which can destroy infected cells and help produce antibodies.

By binding to antigens, antibodies can help destroy pathogens or stop them from entering cells. Also, our immune system creates not only a single antibody, but up to hundreds of different antibodies – or epitopes – each targeting different parts of the antigen.

By comparison, drugs, such as antibiotics or antivirals, are usually small molecules that inhibit a specific enzyme or protein, without which a pathogen cannot survive or replicate. As a result, drug resistance usually only requires mutating a single site. On the other hand, while not impossible, the probability of escape mutations evolving for all, or even most, epitopes targeted by antibodies is vanishingly small for most vaccines.

A graph showing that while antibiotics usually have only one target, vaccines create multiple antibodies binding to a different part of an antigen, making the evolution of resistance more difficult
While antibiotics usually have only one target, vaccines create multiple antibodies binding to a different part of an antigen, making the evolution of resistance more difficult. Célia Souque

With drugs, reducing the probability of resistance can similarly be achieved by using several at the same time – a strategy called combination therapy – which is used to treat HIV and tuberculosis. You could think of the antibodies in your body acting like a massively complex combination therapy, with hundreds of slightly different drugs, thereby reducing the chance of resistance evolving.

Second difference: number of pathogens

Another key difference between antibiotics and vaccines is when they are used and how many pathogens are around. Antibiotics are used to treat an already established infection when millions of pathogens are already in the body. But vaccines are used as prevention. The antibodies they create can act at the very beginning of an infection when pathogen numbers are low. This has important consequences, as resistance is a numbers game. A resistance mutation is unlikely to occur during the replication of a few pathogens, but the chances increase as more pathogens are present.

A graph showing how the more pathogens are present during an infection, the more likely it is a resistance mutation may occur
The more pathogens are present during an infection, the more likely it is a resistance mutation may occur. Célia Souque

This does not mean resistance to vaccines never evolves: a good example is flu. Thanks to its high mutation rate, the flu virus can quickly accumulate enough mutations that antibodies may not recognise it anymore – a process called “antigenic drift”. This explains in part why the flu vaccine has to be changed each year.

What does this tell us about vaccines against SARS-CoV-2? Should we be worried about the new vaccines losing efficacy? Luckily, the novel coronavirus has a proof-reading mechanism that reduces the errors it makes when replicating its genome, and means mutations occur much less frequently than in flu viruses.

Also, it has been confirmed that both the Oxford/AstraZeneca and the Pfizer/BioNTech vaccines can effectively stimulate antibodies binding to multiple epitopes, which should slow down resistance evolution.

But we should still be careful. As mentioned earlier, numbers matter when it comes to resistance. The more viruses that are around – as in a rapidly growing pandemic – the more likely it is one may hit the jackpot and develop mutations resulting in a significant impact on vaccine efficacy. If that’s the case, a new version of the vaccine may be necessary to create antibodies against these mutated viruses. This is also why trying to keep infection numbers low through prevention and contact-tracing is vital to keeping vaccines working for as long as possible.

The Conversation

Celia Souque receives funding from UKRI.

Louis du Plessis is supported by the Oxford Martin School.

Read More

Continue Reading

Government

Looking Back At COVID’s Authoritarian Regimes

After having moved from Canada to the United States, partly to be wealthier and partly to be freer (those two are connected, by the way), I was shocked,…

Published

on

After having moved from Canada to the United States, partly to be wealthier and partly to be freer (those two are connected, by the way), I was shocked, in March 2020, when President Trump and most US governors imposed heavy restrictions on people’s freedom. The purpose, said Trump and his COVID-19 advisers, was to “flatten the curve”: shut down people’s mobility for two weeks so that hospitals could catch up with the expected demand from COVID patients. In her book Silent Invasion, Dr. Deborah Birx, the coordinator of the White House Coronavirus Task Force, admitted that she was scrambling during those two weeks to come up with a reason to extend the lockdowns for much longer. As she put it, “I didn’t have the numbers in front of me yet to make the case for extending it longer, but I had two weeks to get them.” In short, she chose the goal and then tried to find the data to justify the goal. This, by the way, was from someone who, along with her task force colleague Dr. Anthony Fauci, kept talking about the importance of the scientific method. By the end of April 2020, the term “flatten the curve” had all but disappeared from public discussion.

Now that we are four years past that awful time, it makes sense to look back and see whether those heavy restrictions on the lives of people of all ages made sense. I’ll save you the suspense. They didn’t. The damage to the economy was huge. Remember that “the economy” is not a term used to describe a big machine; it’s a shorthand for the trillions of interactions among hundreds of millions of people. The lockdowns and the subsequent federal spending ballooned the budget deficit and consequent federal debt. The effect on children’s learning, not just in school but outside of school, was huge. These effects will be with us for a long time. It’s not as if there wasn’t another way to go. The people who came up with the idea of lockdowns did so on the basis of abstract models that had not been tested. They ignored a model of human behavior, which I’ll call Hayekian, that is tested every day.

These are the opening two paragraphs of my latest Defining Ideas article, “Looking Back at COVID’s Authoritarian Regimes,” Defining Ideas, March 14, 2024.

Another excerpt:

That wasn’t the only uncertainty. My daughter Karen lived in San Francisco and made her living teaching Pilates. San Francisco mayor London Breed shut down all the gyms, and so there went my daughter’s business. (The good news was that she quickly got online and shifted many of her clients to virtual Pilates. But that’s another story.) We tried to see her every six weeks or so, whether that meant our driving up to San Fran or her driving down to Monterey. But were we allowed to drive to see her? In that first month and a half, we simply didn’t know.

Read the whole thing, which is longer than usual.

(0 COMMENTS)

Read More

Continue Reading

Uncategorized

The hostility Black women face in higher education carries dire consequences

9 Black women who were working on or recently earned their PhDs told a researcher they felt isolated and shut out.

Published

on

By

Isolation can make opportunities elusive. fotostorm via Getty Images

Isolated. Abused. Overworked.

These are the themes that emerged when I invited nine Black women to chronicle their professional experiences and relationships with colleagues as they earned their Ph.D.s at a public university in the Midwest. I featured their writings in the dissertation I wrote to get my Ph.D. in curriculum and instruction.

The women spoke of being silenced.

“It’s not just the beating me down that is hard,” one participant told me about constantly having her intelligence questioned. “It is the fact that it feels like I’m villainized and made out to be the problem for trying to advocate for myself.”

The women told me they did not feel like they belonged. They spoke of routinely being isolated by peers and potential mentors.

One participant told me she felt that peer community, faculty mentorship and cultural affinity spaces were lacking.

Because of the isolation, participants often felt that they were missing out on various opportunities, such as funding and opportunities to get their work published.

Participants also discussed the ways they felt they were duped into taking on more than their fair share of work.

“I realized I had been tricked into handling a two- to four-person job entirely by myself,” one participant said of her paid graduate position. “This happened just about a month before the pandemic occurred so it very quickly got swept under the rug.”

Why it matters

The hostility that Black women face in higher education can be hazardous to their health. The women in my study told me they were struggling with depression, had thought about suicide and felt physically ill when they had to go to campus.

Other studies have found similar outcomes. For instance, a 2020 study of 220 U.S. Black college women ages 18-48 found that even though being seen as a strong Black woman came with its benefits – such as being thought of as resilient, hardworking, independent and nurturing – it also came at a cost to their mental and physical health.

These kinds of experiences can take a toll on women’s bodies and can result in poor maternal health, cancer, shorter life expectancy and other symptoms that impair their ability to be well.

I believe my research takes on greater urgency in light of the recent death of Antoinette “Bonnie” Candia-Bailey, who was vice president of student affairs at Lincoln University. Before she died by suicide, she reportedly wrote that she felt she was suffering abuse and that the university wasn’t taking her mental health concerns seriously.

What other research is being done

Several anthologies examine the negative experiences that Black women experience in academia. They include education scholars Venus Evans-Winters and Bettina Love’s edited volume, “Black Feminism in Education,” which examines how Black women navigate what it means to be a scholar in a “white supremacist patriarchal society.” Gender and sexuality studies scholar Stephanie Evans analyzes the barriers that Black women faced in accessing higher education from 1850 to 1954. In “Black Women, Ivory Tower,” African American studies professor Jasmine Harris recounts her own traumatic experiences in the world of higher education.

What’s next

In addition to publishing the findings of my research study, I plan to continue exploring the depths of Black women’s experiences in academia, expanding my research to include undergraduate students, as well as faculty and staff.

I believe this research will strengthen this field of study and enable people who work in higher education to develop and implement more comprehensive solutions.

The Research Brief is a short take on interesting academic work.

Ebony Aya received funding from the Black Collective Foundation in 2022 to support the work of the Aya Collective.

Read More

Continue Reading

Uncategorized

US Economic Growth Still Expected To Slow In Q1 GDP Report

A new round of nowcasts continue to estimate that US economic activity will downshift in next month’s release of first-quarter GDP data. Today’s revised…

Published

on

A new round of nowcasts continue to estimate that US economic activity will downshift in next month’s release of first-quarter GDP data. Today’s revised estimate is based on the median for a set of nowcasts compiled by CapitalSpectator.com.

Output for the January-through-March period is currently projected to soften to a 2.1% increase (seasonally adjusted annual rate). The estimate reflects a substantially softer rise vs. Q4’s strong 3.2% advance, which in turn marks a downshift from Q3’s red-hot 4.9% increase, according to government data.

Today’s revised Q1 estimate was essentially unchanged from the previous Q1 nowcast (published on Mar. 7). At this late date in the current quarter, the odds are relatively high that the current median estimate is a reasonable guesstimate for the actual GDP data that the Bureau of Economic Analysis will publish in late-April.

GDP rising at roughly a 2% pace marks another slowdown from recent quarters, but if the current nowcast is correct it suggests that recession risk remains low. The question is whether the slowdown persists into Q2 and beyond. Given the expected deceleration in growth on tap for Q1, the economy may be flirting with a tipping point for recession later in the year. It’s premature to make such a forecast with high confidence, but it’s a scenario that’s increasingly plausible, albeit speculatively so for now.

Yesterday’s release of retail sales numbers for February aligns with the possibility that even softer growth is coming. Although spending rebounded last month after January’s steep decline, the bounce was lowr than expected.

“The modest rebound in retail sales in February suggests that consumer spending growth slowed in early 2024,” says Michael Pearce, Oxford Economics deputy chief US economist.

Reviewing retail spending on a year-over-year basis provides a clearer view of the softer-growth profile. The pace edged up to 1.5% last month vs. the year-earlier level, but that’s close to the slowest increase in the post-pandemic recovery.

Despite emerging signs of slowing growth, relief for the economy in the form of interest-rate cuts may be further out in time than recently expected, due to the latest round of sticky inflation news this week.

“When the Fed is contemplating a series of rate cuts and is confronted by suddenly slower economic growth and suddenly brisker inflation, they will respond to the new news on the inflation side every time,” says Chris Low, chief economist at FHN Financial. “After all, this is not the first time in the past couple of years consumers have paused spending for a couple of months to catch their breath.”


How is recession risk evolving? Monitor the outlook with a subscription to:
The US Business Cycle Risk Report


Read More

Continue Reading

Trending