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A paradigm shift in immunology highlights the role of vaccines in healthy aging

Dr. Thomas Breuer MD, MSc

Chief Global Health Officer, GSK

Can vaccinations keep declining immune systems in fighting form — even into old age? It’s beginning to look that way.

A growing body of research suggests that vaccines may do more than prevent the specific disease at which they’re aimed. They may have other positive effects, priming the immune system to better prepare it to fight other disease-causing viruses or bacteria throughout life.

It’s called immune fitness, and it means the immune system is resilient and trained to respond appropriately to challenges, such as viruses or other microbes. Just as exercising, avoiding smoking, and eating a healthy diet can reduce the risk of disease, being fully vaccinated at all stages of life can help build immune fitness.

The positive, incidental benefits of vaccines have long been known. Doctors in the 1800s saw that smallpox vaccination improved rashes and reduced susceptibility to measles, syphilis, and other infections.1 In the twenty-first century, we’re starting to understand on the level of the immune system how that happens, and how important it is to change our thinking from a focus only on vaccines for children to vaccination throughout the life-course. This is important to prevent specific diseases but also given the increasing evidence of vaccine effects beyond the targeted disease.

Evidence in support of this concept has mounted during the SARS-CoV-2 pandemic. A study by Cedars-Sinai Health System found that employees who had been given vaccination against tuberculosis called BCG, were significantly less likely to test positive for Covid-19 or to have reported Covid symptoms compared to those who had not received BCG.2 Similarly, a study at Brigham and Women’s Hospital and the Cleveland Clinic found Covid patients who had either measles vaccine (MMR) or tetanus-diphtheria-attenuated pertussis (Tdap) vaccination were less likely to be admitted to intensive care units or to die.3

One possible explanation is that vaccines prompt natural responses that improve immune system resilience by either reprogramming cells belonging to the immune system (so-called trained immunity) or pushing the “reminder button” by boosting pre-existing memory cells generated by prior vaccinations. That may give the immune system a head start when confronted with the Covid virus, SARS-CoV-2, reducing the risk of severe Covid-19 disease, and it may do the same with other pathogens. The research presents an exciting path of exploration into the specific elements of the immune system that make older people so much more vulnerable than the young to Covid-19 and other infectious diseases and suggests that vaccinations can confer protection beyond the target diseases for which they were specifically designed.

Due to the success of infant and childhood vaccination programs in countries with strong public health systems, and the changing demographics of aging populations, the burden of infectious diseases has shifted to older age groups and an increasing proportion of patients with vaccine-preventable diseases are older adults. In the U.S., the number of adults who die from a disease that could have been prevented or mitigated by a vaccine is 350-times higher than the number of such deaths in children, writes Béatrice Laupèze of GSK, Wavre, Belgium, and coauthor of a perspective in the July issue of NPJ Vaccines.4

The Covid-19 pandemic highlighted the vulnerability of older adults to infectious diseases. It is concerning that many adults during the Covid-19 pandemic have put off regular medical care and have fallen behind on recommended immunizations. This not only puts them at risk for diseases such as the flu and pneumococcal pneumonia, but they may also miss out on the opportunity to improve their overall immune fitness.

“We are in the midst of a revolution in immunology,” write the authors of the NPJ Vaccines article. “It is clear that external influences of diet, exercise, combined with good hygiene, and avoidance of toxins such as smoking have far-reaching effects on health including immune health. We now understand that vaccination is an immune event of similar significance…”

Vaccines do not, on their own, turn back the clock on aging immune systems. But this new field of immunology adds to evidence that establishing healthy life-long habits including vaccination through the life course can boost immune fitness and the chance for a long and healthy life.


1 Mayr A. Taking advantage of the positive side-effects of smallpox vaccination. J Vet Med B Infect Dis Vet Public Health. 2004 Jun;51(5):199-201. doi: 10.1111/j.1439-0450.2004.00763.x.

2 Rivas MN, Ebinger JE, Wu M, et al. BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of health care workers. J Clin Invest. 2021 Jan 19;131(2):e145157. doi: 10.1172/JCI145157.

3 Mysore V, Cullere X, Settles ML, et al. Protective heterologous T cell immunity in COVID-19 induced by the trivalent MMR and Tdap vaccine antigens. Med. 2021 Sept 10;2(9):1050-1071. doi: 10.1016/j.medj.2021.08.004.

4 Laupèze B, Del Giudice G, Doherty MT, et al. Vaccination as a preventative measure contributing to immune fitness. npj Vaccines 6, 93 (2021).10.1038/s41541-021-00354-z.