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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Dr. David Fajgenbaum looking through a microscope at his lab.

Courtesy of Fajgenbaum

In late March, just as the COVID-19 pandemic was ramping up in the United States, David Fajgenbaum, a physician-scientist at the University of Pennsylvania, devised a 10-day challenge for his lab: they would sift through 1,000 recently published scientific papers documenting cases of the deadly virus from around the world, pluck out the names of any drugs used in an attempt to cure patients, and track the treatments and their outcomes in a database.

Before late 2019, no one had ever had to treat this exact disease before, which meant all treatments would be trial and error. Fajgenbaum, a pioneering researcher in the field of drug repurposing—which prioritizes finding novel uses for existing drugs, rather than arduously and expensively developing new ones for each new disease—knew that physicians around the world would be embarking on an experimental journey, the scale of which would be unprecedented. His intention was to briefly document the early days of this potentially illuminating free-for-all, as a sidebar to his primary field of research on a group of lymph node disorders called Castleman disease. But now, 11 months and 29,000 scientific papers later, he and his team of 22 are still going strong.

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Julia Sklar
Julia Sklar is a Boston-based independent journalist who covers science, health, and technology. You can follow her on Twitter at @jfsklar.

Leading medical and scientific experts will discuss the latest developments around the COVID-19 vaccines at our March 11th event.

Photo by Daniel Schludi on Unsplash



Thursday, March 11th, 2021 at 12:30pm - 1:45pm EST

On the one-year anniversary of the global declaration of the pandemic, this virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the COVID-19 vaccines. Planned topics include the effect of the new circulating variants on the vaccines, what we know so far about transmission dynamics post-vaccination, how individuals can behave post-vaccination, the myths of "good" and "bad" vaccines as more alternatives come on board, and more. A public Q&A will follow the expert discussion.

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Kira Peikoff
Kira Peikoff is a journalist whose work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.