Senior immunity — what really protects you after 70?

Aim of the study: The aim of this systematic review is to evaluate whether common adult vaccinations are associated with a reduced risk of dementia.

Results: Twenty-one studies (n = 104 031 186 participants) were included. Vaccination against herpes zoster was associated with a reduced risk of any dementia (RR 0.76, 95% CI 0.69-0.83) and Alzheimer's disease (RR 0.53, 95% CI 0.44-0.64). Influenza vaccination was linked to a reduction in dementia risk (RR 0.87, 95% CI 0.77-0.99), as was pneumococcal vaccination (RR 0.64, 95% CI 0.47-0.87) for Alzheimer's disease. Tetanus, diphtheria, pertussis (Tdap) vaccination was also associated with a significant reduction for any dementia (RR 0.67, 95% CI 0.54-0.83). Adult vaccinations, particularly against herpes zoster, influenza, pneumococcus and Tdap, are associated with a lower risk of dementia. Vaccination strategies should be incorporated into public health initiatives for dementia prevention.

Aim of the study: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in immunocompromised adults, including solid organ and hematopoietic stem cell transplant recipients. Following the 2023 licensure of three RSV vaccines for older adults, increasing numbers of immunocompromised individuals have become eligible for vaccination, although these populations were largely excluded from pivotal phase 3 trials.

Results: Humoral immune responses are attenuated and heterogeneous, with seroconversion rates commonly ranging from 30-60% in transplant populations and strongly influenced by time since transplantation, lymphocyte counts, and exposure to antimetabolites such as mycophenolate. Despite reduced antibody responses, first-season vaccine effectiveness against hospitalization is generally between 65% and 75% in immunocompromised adults. Two-season analyses demonstrate waning protection, more pronounced than in immunocompetent individuals. Cellular immune responses, particularly CD4 T-cell responses, may be preserved despite diminished serologic responses, suggesting that antibody measurements alone may underestimate clinical protection. Although immunogenicity is reduced and durability shorter than in immunocompetent adults, RSV vaccination provides meaningful protection against severe disease.

Aim of the study: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials.

Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.

Aim of the study: Adults over the age of 60-65 years suffer disproportionally from seasonal influenza, experiencing high rates of complications, exacerbation of underlying medical comorbidities, and excess mortality. Thus, older adults are an important priority for influenza immunisation campaigns.

Results: Thus, the development of improved vaccines that heighten immune responses and improve effectiveness is an important medical need. To this end, enhanced influenza vaccines specifically targeting this age group have been developed, which seek to overcome the inherent limitations in the immune responses of older adults. Both the licensed high-dose trivalent influenza vaccine (hdTIV) containing fourfold higher antigen contents than standard vaccine, and the MF59® -adjuvanted trivalent influenza vaccine (aTIV) have been proven to be safe and well-tolerated while enhancing the immune response. Healthcare providers for populations of older adults should be advised to routinely use these enhanced influenza vaccines in seasonal immunisation campaigns to provide improved immunity against influenza and its consequences in this particularly susceptible age group.

Aim of the study: The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity.

Results: Recent studies have revealed that the induction of trained immunity is associated with a bias toward granulopoiesis in bone marrow hematopoietic progenitor cells, but it is unknown whether BCG vaccination also leads to functional reprogramming of mature neutrophils. Here, we show that BCG vaccination of healthy humans induces long-lasting changes in neutrophil phenotype, characterized by increased expression of activation markers and antimicrobial function. The enhanced function of human neutrophils persists for at least 3 months after vaccination and is associated with genome-wide epigenetic modifications in trimethylation at histone 3 lysine 4. Functional reprogramming of neutrophils by the induction of trained immunity might offer novel therapeutic strategies in clinical conditions that could benefit from modulation of neutrophil effector function.

Aim of the study: Psychological distress and biobehavioral vulnerability (e.g., arising from being older or sedentary) have independently predicted immune responses to influenza vaccination in older adults. Recent research examining basal inflammatory markers suggests that, rather than having additive effects, distress and vulnerability interact with each other.

Results: BMI interacted with stable individual differences in distress to predict antibody response (t(132)=3.09, p<0.003), such that only the combination of low BMI and low distress was associated with a more robust antibody response. Likewise, changes in physical activity over time interacted with changes in distress (t(156)=2.96, p<0.004), such that only the combination of increased physical activity and decreased distress was associated with a more robust antibody response. Finally, there was a smaller tendency for age to interact with stable individual differences in distress (t(130)=2.46, p<0.015), such that distress was more strongly associated with post-vaccination IL-6 at older ages. The synergistic effects of distress and other forms of vulnerability are an important direction for future research and a target for interventions to improve immunological health in older adults.

Aim of the study: Institutionalized and community-dwelling older adults have been greatly impacted by the COVID-19 pandemic with increased morbidity and mortality. The advent of vaccines and their widespread use in this population has brought about a dramatic turnaround in COVID-19 outcomes.

Results: The advent of vaccines and their widespread use in this population has brought about a dramatic turnaround in COVID-19 outcomes. The immunogenicity and effectiveness of the various vaccine options worldwide will be discussed. Optimizing vaccine usage will remain crucial to maximize protection due to reduced initial immunity, the emergence of variant strains, and the waning of immunity over time. There are also lessons learned specific to older populations for future pandemics of novel pathogens where there is minimal to no prior immunity.

Aim of the study: Upper respiratory tract infections (URTIs) are common viral illnesses whose burden increases with age-related declines in innate immunity. Maitake mushrooms (Grifola frondosa) have immunomodulatory properties, but evidence in healthy humans, particularly regarding age-related innate immune responses, remains limited.

Results: While the overall incidence of URTI episodes did not differ between groups, symptom-specific analyses suggested strain-dependent differences. Y10M supplementation was associated with fewer cumulative days of fever and runny nose in both age groups and with sore throat in young adults, whereas C5304 showed limited effects. Notably, Y10M was associated with changes in innate immune parameters in middle-aged/older adults, including increased plasmacytoid dendritic cell frequency, activation of conventional dendritic cells, and upregulation of type I interferon-related gene expression and IL12A following ex vivo stimulation. These findings suggest that dietary maitake supplementation, particularly with the Y10M strain, may reduce the cumulative burden of selected URTI-related symptoms and modulate antiviral innate immune responses in healthy adults, with effects that may differ by strain and age cohort.