Scientists at The Jackson Laboratory (JAX) and UConn Health are working to understand why vaccines are less effective in some older adults. With the aging population at a higher risk for severe infections and diseases, such as pneumonia and meningitis, it is crucial to determine the factors contributing to decreased vaccine efficacy.
Streptococcus pneumoniae, a dangerous bacterial pathogen, causes diseases that affect infants and older adults. The case-fatality rates for pneumococcal infections increase with age, but the reasons behind this phenomenon are not well understood.
Thankfully, vaccines like PPSV23 (Pneumovax) have proven to be effective in older adults. However, they do not offer the same level of protection as they do in younger adults. Scientists have developed conjugated vaccines, such as PCV13 (Prevnar), which combine the polysaccharide found on the surface of S. pneumoniae with a protein. This combination induces a stronger immune response and provides better protection.
Despite these advancements, vaccine responses decline with age, and it remains unclear which of the two vaccines is preferable for subpopulations of older adults.
To address these gaps in knowledge, a team of researchers led by JAX Associate Professor Duygu Ucar, UConn Health Professor George Kuchel, and Jacques Banchereau from Immunoledge conducted a study. They vaccinated a cohort of 39 older adults, aged 60 and above, who had not previously received pneumococcal vaccines. The researchers examined the pre- and post-vaccine immune characteristics to identify the factors influencing variable responses to the two vaccines.
The findings, published in Nature Immunology, highlight distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults. The study identifies predictors that could potentially improve vaccination strategies and lead to more effective interventions.
Ucar explains that understanding which vaccine will elicit a strong response in individuals allows for stratification of the population to enhance vaccine efficacy. Additionally, finding ways to modulate an individual’s immune characteristics prior to vaccination may improve outcomes at the individual level.
During the study, all participants received a single dose of PPSV23 or PCV13. Blood samples were taken before and after vaccination to gather longitudinal data. While overall responses to both vaccines were comparable, there were clear differences in baseline immune phenotypes between individuals who had strong or weak responses.
The study revealed that the baseline abundance of two specific T cell types, Th1 and Th17 cells, played a crucial role in the responses to PCV13. Higher levels of Th1 cells were positively associated with PCV13 response strength, while higher levels of Th17 cells were negatively associated. Interestingly, women had a higher frequency of Th1 cells and a lower frequency of Th17 cells compared to men, resulting in a stronger response to the PCV13 vaccine.
The researchers also discovered a gene module associated with reduced PCV13 responses prior to vaccination. This gene module, called the CYTOX signature, was linked to mature CD16+ natural killer (NK) cells. Participants who had weak responses to PCV13 had a higher abundance of CD16+ NK cells compared to those with strong responses. The CYTOX signature did not affect responses to the PPSV23 vaccine, indicating distinct gene sets predict responses to each vaccine.
Kuchel emphasizes that a one-size-fits-all approach does not work for older patients. The study’s findings offer remarkable opportunities for precision gerontology, providing more effective care models for older adults. The researchers also note that the predictors for the two classes of pneumococcal vaccines are distinct and independent from each other, despite using the same polysaccharides to stimulate the immune response.
The study’s results have significant implications for refining vaccine strategies for older adults, not only for pneumococcal vaccines but potentially for other vaccines as well. By identifying specific pre-vaccination characteristics, individuals can be stratified to receive the vaccine that works best for them. This personalized approach aims to better protect older adults from infection and disease.
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