Drugs That Trick Older People’s Bodies to Behave Younger Might Boost the Effectiveness of a COVID-19 Vaccine

Because vaccination may be less effective in older people, it is imperative to test now whether immune boosters could help the efficacy of a COVID-19 vaccine in the elderly.

(© thodonal/Adobe)

In our April 23rd editorial for this magazine, we argued that addressing the COVID-19 pandemic requires that we both fight the SARS-CoV-2 virus and fortify the human hosts who are most vulnerable to it.

Two recent phase 2 studies in older adults have suggested that a new category of drugs called rapalogues can in some cases increase the immunization capacity of older adults.

Because people over 70 account for more than 80 percent of reported COVID-19 deaths globally, this means we must do everything possible to protect our elders.

A range of recent studies have suggested that systemic knobs might metaphorically be turned to slow the cellular aging process, making us better able to fight off the many diseases correlated with aging. These types of systemic changes might be used to stem the specific decline in immunity caused by aging and to increases the biological capacity of elderly people to effectively fight viral infection.

But while helping make older people more resilient in the face of a viral infection is critical, that's not the only way geroscience can help in our fight against this deadly pandemic.

As we move toward hopefully developing one or more COVID-19 vaccines, researchers must more fully appreciate the ways in which traditional vaccines can be less effective in older people than in younger ones.

Repeated studies have shown that the flu vaccine, for example, has lower efficacy in older people than in younger ones. Older people tend to develop fewer antibodies after being vaccinated because a subset of their white blood cells, called T cells, have become less responsive over time. Some inflammatory peptides that increase with aging are also preventing the action of those T cells.

This is why there's a distinct possibility that a future COVD-19 vaccine, particularly one utilizing the traditional attenuated virus approach, could be less effective in older people than in younger ones.

Given the extreme urgency of developing vaccines that work well for everyone, we need to make sure that researchers are exploring all of the ways our elders can be best protected. While generating a vaccine that works equally well for people of all ages would be ideal, we can't count on that.

One way to bridge this gap might be to trick the bodies of older people into behaving as if they are younger just at the moment what a vaccine is delivered by giving them pre-immunization boosters.

Two recent phase 2 studies in older adults have suggested that a new category of drugs called rapalogues can in some cases increase the immunization capacity of older adults. Use of the drug for a short time period before flu shot immunization increased the antibody production for the flu and resulted in a 52 percent decrease in the occurrence of severe diseases needing medical help or hospitalization. This short-term pre-immunization intervention can also decrease the severity of serious respiratory tract infections, the deadliest manifestations of COVID-19, by similar magnitude. These patients also had almost half the incidence of the non-COVID-19 coronaviruses associated with the common cold.

The fact that those people were protected by treatment before hospitalization suggests metformin may have a role in boosting the vaccination of older people.

An inexpensive generic drug called metformin similarly targets the decline in immunity and inflammation (and extends health span and lifespan) in animals and has been used for decades to protect against the flu. A recent paper from a hospital in Wuhan, China showed that mortality of elderly COVID-19 diabetic patients on metformin was 25 percent less than that of patients with diabetes but not on metformin.

Another study from the U.S. showed that COVID-19 patients on metformin had a 20 percent decrease in mortality and lower inflammation. The fact that those people were protected by treatment before hospitalization suggests metformin may have a role in boosting the vaccination of older people.

We don't yet know whether rapalogues or metformin could be used as COVID-19 immunization boosters, not least because we don't have those vaccines. But we can and should make sure that all vaccine trials including older subjects also consider offering a subset of those subjects appropriate doses of rapalogues or metformin to explore whether doing so can boost the efficacy of a given vaccine.

If we weren't in the middle of the worst pandemic in a century, we would have more time to test our vaccines slowly and sequentially. In the context of the current crisis, however, testing whether immunization boosters might increase the efficacy of potential COVID-19 vaccines for older adults is at the very least a hypothesis worth exploring.

Jamie Metzl And Nir Barzilai
Jamie Metzl is a member of the World Health Organization international advisory committee on human genome editing, a Singularity University Exponential Medicine faculty member, and the author of Hacking Darwin: Genetic Engineering and the Future of Humanity (paperback release April 7). @jamiemetzl. Nir Barzilai is a Professor of Medicine and Genetics and the Director of the Institute for Aging research at Albert Einstein College of Medicine, the Scientific Director of the American Federation for Aging Research and the author of Age Later: Healthspan, Lifespan, and the New Science of Longevity (June 2020). Dr. Nir Barzilai is the director of the Institute for Aging Research at the Albert Einstein College of Medicine and the Director of the Paul F. Glenn Center for the Biology of Human Aging Research and of the National Institutes of Health’s (NIH) Nathan Shock Centers of Excellence in the Basic Biology of Aging. He is the Ingeborg and Ira Leon Rennert Chair of Aging Research, professor in the Departments of Medicine and Genetics, and member of the Diabetes Research Center and of the Divisions of Endocrinology & Diabetes and Geriatrics. Dr. Barzilai’s research interests are in the biology and genetics of aging.
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Astronaut and Expedition 64 Flight Engineer Soichi Noguchi of the Japan Aerospace Exploration Agency displays Extra Dwarf Pak Choi plants growing aboard the International Space Station. The plants were grown for the Veggie study which is exploring space agriculture as a way to sustain astronauts on future missions to the Moon or Mars.

Johnson Space Center/NASA

Astronauts at the International Space Station today depend on pre-packaged, freeze-dried food, plus some fresh produce thanks to regular resupply missions. This supply chain, however, will not be available on trips further out, such as the moon or Mars. So what are astronauts on long missions going to eat?

Going by the options available now, says Christel Paille, an engineer at the European Space Agency, a lunar expedition is likely to have only dehydrated foods. “So no more fresh product, and a limited amount of already hydrated product in cans.”

For the Mars mission, the situation is a bit more complex, she says. Prepackaged food could still constitute most of their food, “but combined with [on site] production of certain food products…to get them fresh.” A Mars mission isn’t right around the corner, but scientists are currently working on solutions for how to feed those astronauts. A number of boundary-pushing efforts are now underway.

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Payal Dhar
Payal is a writer based in New Delhi who has been covering science, technology, and society since 1998.

A brain expert weighs in on the cognitive biases that hold us back from adjusting to the new reality of Omicron.

Photo by Joshua Sortino on Unsplash

We are sticking our heads into the sand of reality on Omicron, and the results may be catastrophic.

Omicron is over 4 times more infectious than Delta. The Pfizer two-shot vaccine offers only 33% protection from infection. A Pfizer booster vaccine does raises protection to about 75%, but wanes to around 30-40 percent 10 weeks after the booster.

The only silver lining is that Omicron appears to cause a milder illness than Delta. Yet the World Health Organization has warned about the “mildness” narrative.

That’s because the much faster disease transmission and vaccine escape undercut the less severe overall nature of Omicron. That’s why hospitals have a large probability of being overwhelmed, as the Center for Disease Control warned, in this major Omicron wave.

Yet despite this very serious threat, we see the lack of real action. The federal government tightened international travel guidelines and is promoting boosters. Certainly, it’s crucial to get as many people to get their booster – and initial vaccine doses – as soon as possible. But the government is not taking the steps that would be the real game-changers.

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Gleb Tsipursky
Dr. Gleb Tsipursky is an internationally recognized thought leader on a mission to protect leaders from dangerous judgment errors known as cognitive biases by developing the most effective decision-making strategies. A best-selling author, he wrote Resilience: Adapt and Plan for the New Abnormal of the COVID-19 Coronavirus Pandemic and Pro Truth: A Practical Plan for Putting Truth Back Into Politics. His expertise comes from over 20 years of consulting, coaching, and speaking and training as the CEO of Disaster Avoidance Experts, and over 15 years in academia as a behavioral economist and cognitive neuroscientist. He co-founded the Pro-Truth Pledge project.