As described in iScience, the team added the Pfizer/BioNTech COVID mRNA vaccine to blood samples from people in different age groups. Extensive tests, including systems biology approaches such as proteomics, then measured immune activation in response to the vaccine.
This approach identified muted innate immune responses in people over age 60 as compared with those age 18 to 50. In particular, older adults showed an impaired ability to support Th1 immunity, with diminished early inflammatory responses. They also had lower levels of four key cytokines (CXCL10, IL-1RA, IFN-gamma, and CCL4), biomarkers indicating a more robust immune response including T cell-mediated immunity.
“The early innate response to mRNA vaccines is critical in instructing the adaptive immune system, triggering maturation of CD4 T cells and supporting downstream cellular and antibody responses that are long-lived,” explains Brook.
The lower initial response observed with advancing age, also seen in mice, may explain why immunity induced by mRNA and other types of vaccines may wane more quickly in older adults, the researchers say.
While mouse studies have been a gold standard for research, they are expensive, time-consuming, and don’t always capture human immune biology accurately. The FDA Modernization Act 2.0, signed into law in 2022, now allows for alternatives to animal testing, including human cell and organoid models alongside systems biology approaches.
Levy emphasizes that their MEMPHIS test system, for which they’ve filed a patent, is an exemplar of this new approach. The system provides a nimbler way to predict age-specific human vaccine responses, allowing multiple vaccine doses and vaccine adjuvants — which boost the immune response — to be tested simultaneously in samples from the same person.
“If we could elicit a young-adult-like innate immune response in an elder, we might be able to provide better, more durable protection,” says Brook.
