T-Cell Responses to Influenza Vaccination in Patients With Heart Failure
T-Cell Responses to Influenza Vaccination in Patients With Heart Failure
Study objective. To determine whether T-cell immune responses to influenza vaccination in patients with chronic heart failure (CHF) are less vigorous than the responses of healthy control subjects.
Design. Prospective, single-center study.
Setting. University hospital and research laboratory.
Participants. Eighteen adults with stable CHF receiving optimal treatment and 16 healthy control subjects.
Intervention. Participants were immunized with the 2006–2007 trivalent inactivated (killed) influenza vaccine during October–December of 2006.
Measurements and main results. Blood samples were taken from the participants before and 2–4 weeks after vaccination to measure antibody titers, which were measured with a hemagglutination inhibition assay, then 3–4 months after vaccination to assess T-cell responses, measured by using the trans vivo delayed-type hypersensitivity method. As part of this method, which mimics physiologic conditions, peripheral blood mononuclear cells were isolated from the blood samples. The cells were mixed with influenza vaccine antigens A/H1N1, A/H3N2, and B type and injected into the footpads of SCID mice (mice with severe combined immunodeficiency), as their resulting swelling is an index of human T-cell sensitization. Median Tcell–mediated immune responses to A/H3N2 were less vigorous in patients with CHF than in control subjects (62.5 vs 87.5 μm, unadjusted p=0.031, ageadjusted p=0.006). Median responses to A/H1N1 were not significantly different between the groups (56.3 vs 75 μm, p=0.11). Median responses to B type were also similar between the groups (62.5 vs 75 μm, p=0.47). All participants mounted an antibody response to the influenza vaccine.
Conclusion. Patients with CHF had reduced T-cell responses to the influenza vaccine compared with healthy control subjects, as demonstrated by a lower response to A/H3N2, the newest antigen in the 2006–2007 vaccine. However, differences in T-cell immune responses to the A/H1N1 and B type strains were not found to be significant between the two groups, which suggests that patients with CHF can mount an appropriate response to vaccine antigens to which they have been previously exposed, but less so to new antigens. These findings suggest that patients with CHF may be at increased risk for influenza infection, and clinicians may want to investigate other or additional strategies for influenza vaccination.
Chronic heart failure (CHF) predisposes individuals to influenza infection and its complications. Excess mortality observed during winter months in individuals with CHF is attributed to influenza. Vaccination against influenza infection decreases heart-related hospital admissions, acute CHF exacerbations, and all-cause mortality. Despite widespread influenza vaccination programs, overall influenza-related hospitalizations and mortality rates are rising, particularly in patients with cardiac disease.
Older adults and persons with cardiac disease or other comorbidities and treatments that render them immunocompromised are at elevated risk for influenza infection despite vaccination because of their reduced antibody and cell-mediated vaccine responses. In patients with CHF, an upregulated sympathetic nervous system may activate β2-adrenergic receptors, reducing the cytokine production necessary for vaccine immune response. Therefore, it is logical that patients with CHF have higher influenza-related morbidity and mortality rates compared with individuals without cardiac disease, potentially due to upregulation of adrenergic pathways.
Most adults develop both humoral antibody and T-cell immune responses after influenza vaccination, indicating that both type 1 (T helper 1) and type 2 (T helper 2) responses occur after influenza immunization. The most widely accepted indicators of an immune response to influenza vaccine are seroconversion and seroprotection, which refer to changes in antibody titers in reaction to one of the three viral strains used in the vaccine. However, postvaccination antibody titers as a measure of vaccine effectiveness in protecting against influenza illness in older adults do not measure cell-mediated immunity, which is particularly affected by disease and increasing age. Previous research, including our own work, into the immune responses of CHF was based on in vitro methods to measure T-cell–mediated response that can be highly variable.
In this study, we measured T-cell responses to influenza vaccination using trans vivo delayedtype hypersensitivity, a novel method to investigate T-cell function and sensitization under physiologic conditions. We hypothesized that patients with CHF mount less vigorous Tcell responses to influenza vaccination compared with those of healthy individuals.
Abstract and Introduction
Abstract
Study objective. To determine whether T-cell immune responses to influenza vaccination in patients with chronic heart failure (CHF) are less vigorous than the responses of healthy control subjects.
Design. Prospective, single-center study.
Setting. University hospital and research laboratory.
Participants. Eighteen adults with stable CHF receiving optimal treatment and 16 healthy control subjects.
Intervention. Participants were immunized with the 2006–2007 trivalent inactivated (killed) influenza vaccine during October–December of 2006.
Measurements and main results. Blood samples were taken from the participants before and 2–4 weeks after vaccination to measure antibody titers, which were measured with a hemagglutination inhibition assay, then 3–4 months after vaccination to assess T-cell responses, measured by using the trans vivo delayed-type hypersensitivity method. As part of this method, which mimics physiologic conditions, peripheral blood mononuclear cells were isolated from the blood samples. The cells were mixed with influenza vaccine antigens A/H1N1, A/H3N2, and B type and injected into the footpads of SCID mice (mice with severe combined immunodeficiency), as their resulting swelling is an index of human T-cell sensitization. Median Tcell–mediated immune responses to A/H3N2 were less vigorous in patients with CHF than in control subjects (62.5 vs 87.5 μm, unadjusted p=0.031, ageadjusted p=0.006). Median responses to A/H1N1 were not significantly different between the groups (56.3 vs 75 μm, p=0.11). Median responses to B type were also similar between the groups (62.5 vs 75 μm, p=0.47). All participants mounted an antibody response to the influenza vaccine.
Conclusion. Patients with CHF had reduced T-cell responses to the influenza vaccine compared with healthy control subjects, as demonstrated by a lower response to A/H3N2, the newest antigen in the 2006–2007 vaccine. However, differences in T-cell immune responses to the A/H1N1 and B type strains were not found to be significant between the two groups, which suggests that patients with CHF can mount an appropriate response to vaccine antigens to which they have been previously exposed, but less so to new antigens. These findings suggest that patients with CHF may be at increased risk for influenza infection, and clinicians may want to investigate other or additional strategies for influenza vaccination.
Introduction
Chronic heart failure (CHF) predisposes individuals to influenza infection and its complications. Excess mortality observed during winter months in individuals with CHF is attributed to influenza. Vaccination against influenza infection decreases heart-related hospital admissions, acute CHF exacerbations, and all-cause mortality. Despite widespread influenza vaccination programs, overall influenza-related hospitalizations and mortality rates are rising, particularly in patients with cardiac disease.
Older adults and persons with cardiac disease or other comorbidities and treatments that render them immunocompromised are at elevated risk for influenza infection despite vaccination because of their reduced antibody and cell-mediated vaccine responses. In patients with CHF, an upregulated sympathetic nervous system may activate β2-adrenergic receptors, reducing the cytokine production necessary for vaccine immune response. Therefore, it is logical that patients with CHF have higher influenza-related morbidity and mortality rates compared with individuals without cardiac disease, potentially due to upregulation of adrenergic pathways.
Most adults develop both humoral antibody and T-cell immune responses after influenza vaccination, indicating that both type 1 (T helper 1) and type 2 (T helper 2) responses occur after influenza immunization. The most widely accepted indicators of an immune response to influenza vaccine are seroconversion and seroprotection, which refer to changes in antibody titers in reaction to one of the three viral strains used in the vaccine. However, postvaccination antibody titers as a measure of vaccine effectiveness in protecting against influenza illness in older adults do not measure cell-mediated immunity, which is particularly affected by disease and increasing age. Previous research, including our own work, into the immune responses of CHF was based on in vitro methods to measure T-cell–mediated response that can be highly variable.
In this study, we measured T-cell responses to influenza vaccination using trans vivo delayedtype hypersensitivity, a novel method to investigate T-cell function and sensitization under physiologic conditions. We hypothesized that patients with CHF mount less vigorous Tcell responses to influenza vaccination compared with those of healthy individuals.
