Richard Banks

Age-related differences in polyfunctional T cell responses

BackgroundA reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses. In this study we compared the individual and polyfunctional expression of IFN-γ, MIP-1α, TNF-α, perforin, and IL-2 by T cell subsets, including the newly described stem cell like memory T cells (TSCM), in response to stimulation with superantigen staphylococcal enterotoxin B (SEB) in older (median age 80, n = 23) versus younger (median age 27; n = 23) adults.ResultsOlder age was associated with a markedly lower frequency of CD8+ naïve T cells (11% vs. 47%; p < 0.0001) and an expansion in memory T cell subsets including central memory (p < 0.05), effector memory and effector T cells (p < 0.001 for both). There was also a decline in CD4+ naïve T cells in older subjects (33% vs. 45%; p = 0.02). There were no differences in frequencies or polyfunctional profiles of TSCM between groups. CD8+ naïve cells in the older group had increased expression of all functional parameters measured compared to the younger subjects and exhibited greater polyfunctionality (p = 0.04). CD4+ naïve T cells in the older group also showed greater polyfunctionality with a TNF-α and IL-2 predominance (p = 0.005). CD8+ effector memory and effector T cells exhibited increased polyfunctionality in the older group compared with younger (p = 0.01 and p = 0.003).ConclusionsThese data suggest that aging does not have a negative effect on polyfunctionality and therefore this is likely not a major contributor to the immunesenescence described with aging.

Characterization of MHC-II antigen presentation by B cells and monocytes from older individuals

In this study we examine the effects of aging on antigen presentation of B cells and monocytes. We compared the antigen presentation function of peripheral blood B cells from young and old subjects using a system that specifically measures the B cell receptor (BCR)-mediated MHC-II antigen presentation. Monocytes were studied as well. Overall the mean magnitude of antigen presentation of soluble antigen and peptide was not different in older and younger subjects for both B cells and monocytes. Older subjects, however, showed increased heterogeneity of BCR-mediated antigen presentation by their B cells. The magnitude and variability of peptide presentation, which do not require uptake and processing, were the same between groups. Presentation by monocytes had similar variability between the older and younger subjects. These data suggest that poor B cell antigen processing, which results in diminished presentation in some older individuals may contribute to poor vaccine responses.

Preexisting immunity, not frailty phenotype, predicts influenza postvaccination titers among older veterans

ABSTRACT Both preexisting immunity to influenza and age have been shown to be correlates of influenza vaccine responses. Frailty, an indicator of functional impairment in older adults, was also shown in one study to predict lower influenza vaccine responses among nonveterans. In the current study, we aimed to determine the associations between frailty, preexisting immunity, and immune responses to influenza vaccine among older veterans. We studied 117 subjects (age range, 62 to 95 years [median age, 81 years]), divided into three cohorts based on the Fried frailty test, i.e., nonfrail (NF) (n = 23 [median age, 68 years]), prefrail (n = 50 [median age, 80 years]), and frail (n = 44 [median age, 82 years]), during the 2010-2011 and 2011-2012 influenza seasons. Subjects received the seasonal trivalent inactivated influenza vaccine, and baseline and postvaccination samples were obtained. Anti-influenza humoral immunity, as measured by hemagglutination inhibition (HI) and microneutralization assays, was measured for influenza B, A(H1N1)pdm09, and A(H3N2) viruses. Postvaccination titers were not different between frail and NF subjects overall in this older subset of veterans. However, preexisting HI titers were strongly correlated with postvaccination titers among all functional status groups. When microneutralization titers were compared, the association between preexisting immunity and vaccine responses varied by frailty status, with the strongest correlation being observed for the NF group. In conclusion, preexisting immunity rather than frailty appeared to predict postvaccination titers in this older veteran cohort.

A virtual clinic improves pneumococcal vaccination for asplenic veterans at high risk for pneumococcal disease

We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients.

A virtual clinic improves pneumococcal vaccination coverage among patients living with HIV at a Veterans Affairs Medical Center

ABSTRACT People living with the human immunodeficiency virus (HIV) should receive pneumococcal vaccinations as part of their routine health maintenance. Our goal was to create a “virtual clinic” to help increase rates of pneumococcal vaccination among people living with HIV without adding substantially to the workload of primary providers. We used administrative data from our Veterans Affairs (VA) medical center to identify a cohort of veterans living with HIV who were not current with either the 13-valent pneumococcal conjugate vaccine (PCV13), the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or both. We enrolled these individuals (n = 99) into a virtual clinic, notified providers via the electronic medical record and mailed letters to the veterans recommending they receive a pneumococcal vaccine. We also wrote orders for the appropriate pneumococcal vaccine that expired after 90 days. Among the virtual clinic cohort, 38% (38/99) of patients received the recommended vaccine within 180 days. Concurrent with our intervention, the Veterans Health Administration deployed a system-wide pneumococcal vaccine clinical reminder that incorporated recent PCV13 recommendations. To discern any effect of the virtual clinic beyond that of the clinical reminder, we compared the rate of PCV13 vaccinations among all HIV-positive veterans at our institution to the equivalent population from 2 other VA medical centers in Ohio. With consideration of the VHA’s system-wide clinical reminder, the proportion of HIV-positive patients who received PCV13 in the first 90 days following the virtual clinic intervention was greater at our facility compared to another Ohio VA medical center (P < 0.05). The virtual clinic improved the pneumococcal vaccine coverage among HIV-positive veterans. These outcomes suggest that even in conjunction with a system-wide clinical reminder, the virtual clinic strategy improves vaccination rates among a high-risk population.

A pilot study using telehealth to implement antimicrobial stewardship at two rural Veterans Affairs medical centers

OBJECTIVE To test the feasibility of using telehealth to support antimicrobial stewardship at Veterans Affairs medical centers (VAMCs) that have limited access to infectious disease-trained specialists. DESIGN A prospective quasi-experimental pilot study. SETTING Two rural VAMCs with acute-care and long-term care units.InterventionAt each intervention site, medical providers, pharmacists, infection preventionists, staff nurses, and off-site infectious disease physicians formed a videoconference antimicrobial stewardship team (VAST) that met weekly to discuss cases and antimicrobial stewardship-related education. METHODS Descriptive measures included fidelity of implementation, number of cases discussed, infectious syndromes, types of recommendations, and acceptance rate of recommendations made by the VAST. Qualitative results stemmed from semi-structured interviews with VAST participants at the intervention sites. RESULTS Each site adapted the VAST to suit their local needs. On average, sites A and B discussed 3.5 and 3.1 cases per session, respectively. At site A, 98 of 140 cases (70%) were from the acute-care units; at site B, 59 of 119 cases (50%) were from the acute-care units. The most common clinical syndrome discussed was pneumonia or respiratory syndrome (41% and 35% for sites A and B, respectively). Providers implemented most VAST recommendations, with an acceptance rate of 73% (186 of 256 recommendations) and 65% (99 of 153 recommendations) at sites A and B, respectively. Qualitative results based on 24 interviews revealed that participants valued the multidisciplinary aspects of the VAST sessions and felt that it improved their antimicrobial stewardship efforts and patient care. CONCLUSIONS This pilot study has successfully demonstrated the feasibility of using telehealth to support antimicrobial stewardship at rural VAMCs with limited access to local infectious disease expertise.