T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly

Abstract

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-γ:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

Elderly men with moderate and intense training lifestyle present sustained higher antibody responses to influenza vaccine

“…However, the influence of the vaccine on the prevalence of flu-like episodes may be difficult to estimate because of the heterogeneous etiology of these episodes in our setting, with only a small percentage related to influenza virus, even in non-vaccinated populations, <5 % outside the peak season and <25 % at the peak season (Sistema de Vigilância Epidemiológica da Gripe 2012, Brazil). We also did not assess cell-mediated immune responses to the vaccine, which are also affected by aging (McElhaney et al 2006). Some of the subjects enrolled in this study participated in a parallel study of the effects of aging on T cells, and in fact, there were several aspects of the biology of these cells that were improved in the trained groups [Silva and de Araújo, manuscript in preparation]; however, the cell-mediated responses to influenza antigens were not examined.…”

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

“…Although functional antibody responses are an accepted correlate for vaccine induced protection for vaccine licensure purposes [26], there are increasing reports that T-cell responses are important [27] and may be better correlates of vaccine protection especially in the elderly [28]. Whole virus vaccine may induce a more efficient cellular response than split or sub-unit vaccines [29,30] and this may be critical in preventing severe disease and death if not critical for prevention of infection.…”

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

“…In SLE, antibody responses to influenza vaccination are diminished (6), but cell-mediated responses have not been assessed. The latter are relevant, because it has been shown that in certain groups, such as the elderly, cellmediated responses to influenza vaccination can be a marker of clinical protection, independent from antibody responses (7). The most frequently used vaccine formulations are split virus or subunit vaccines.…”