Improvement of the immunoglobulin subclass response to influenza vaccine in elderly nursing-home residents by the use of high-dose vaccines

Remarque, Edmond J.; Beek, W.C.A. van; Ligthart, G. J.; Borst, Rowie; Nagelkerken, Lex; Palache, Abraham; Sprenger, M. J. W.; Masurel, N.

doi:10.1016/0264-410x(93)90311-k

Cited by 55 publications

(25 citation statements)

References 26 publications

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“…It is possible that a booster of influenza vaccine, which is used in the pediatric population, may increase the cellular immune responses in the elderly. Of interest, studies reported that an increased dose of influenza vaccine improved humoral immune responses to influenza virus in the elderly (39,40). However, the impact of an increased dose and/or a booster of influenza vaccine on the T cell immune response and the protection rate has not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Kang

Hong

Nolasco

et al. 2004

The Journal of Immunology

182

113

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We investigated the relationship of memory CD4+ T cells with the evolution of influenza virus-specific CD4+ T cell responses in healthy young and elderly people. Elderly individuals had a similar frequency of CD69+CD4+ T cells producing IFN-γ and TNF-α at 1 wk, but a lower frequency of these CD4+ T cells at 3 mo after influenza vaccination. Although the elderly had a higher frequency of central memory (CM; CCR7+CD45RA−) CD4+ T cells, they had a significantly lower frequency of effector memory (EM; CCR7−CD45RA−) CD4+ T cells, and the frequency of the latter memory CD4+ T cells positively correlated with the frequency of influenza virus-specific CD69+CD4+ T cells producing IFN-γ at 3 mo. These findings indicate that the elderly have an altered balance of memory CD4+ T cells, which potentially affects long term CD4+ T cell responses to the influenza vaccine. Compared with the young, the elderly had decreased serum IL-7 levels that positively correlated with the frequency of EM cells, which suggests a relation between IL-7 and decreased EM cells. Thus, although the healthy elderly mount a level of CD4+ T cell responses after vaccination comparable to that observed in younger individuals, they fail to maintain or expand these responses. This failure probably stems from the alteration in the frequency of CM and EM CD4+ T cells in the elderly that is related to alteration in IL-7 levels. These findings raise an important clinical question about whether the vaccination strategy in the elderly should be modified to improve cellular immune responses.

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Section: Discussionmentioning

confidence: 99%

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Kang

Hong

Nolasco

et al. 2004

The Journal of Immunology

182

113

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“…There may also be more subtle differences between the responses of young and old individuals, such as a selective impairment of particular classes of antibody production, for example, of IgG1 responses to inactivated influenza virus vaccine in the elderly (447,448). This possibly reflects less efficient or altered T cell help.…”

Section: Vaccination (See Also Section 41)mentioning

confidence: 99%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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“…IgG antibodies to the vaccine strains were determined by ELISA [Remarque et al, 1993[Remarque et al, , 1998. The antibody levels as determined by ELISA show good agreement with the haemagglutination inhibition test.…”

Section: Laboratory Measurementsmentioning

confidence: 79%

“…The protection afforded by the current in¯uenza vaccines, however, is often suboptimal in frail elderly people. This is illustrated by outbreaks of in¯uenza A in nursing homes despite vaccination [Coles et al, 1992;Nicholson et al, 1992] and by poor antibody responses after vaccination [Nicholson et al, 1992;Remarque et al, 1993]. Moreover, in frail elderly patients, antibody responses are dependent on the health status [Remarque et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

“…The lower initial antibody levels as observed in frail elderly patients after vaccination with a standard vaccine dose [Remarque et al, 1993[Remarque et al, , 1996 combined with a decline in antibody levels over time makes this group more susceptible to infection. An adapted vaccination regime, that yields higher antibody levels, is necessary in elderly nursing home patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Randomized controlled trial of seroresponses to double dose and booster influenza vaccination in frail elderly subjects

Eijndhoven¹,

Cools²,

Westendorp³

et al. 2001

J. Med. Virol.

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Responses to influenza vaccination are poor in frail elderly subjects who suffer the greatest morbidity and mortality due to infection. Therefore, a randomized clinical trial was performed to determine the effect of a double dose and booster vaccination on antibody responses after influenza vaccination. A total of 815 patients (median age 83 years, median disability score 8, median disease categories 2 and median number of medications 4) residing in 14 nursing homes in the Netherlands were vaccinated during the influenza season 1997-98. The first vaccine dose (15 or 30 microg) was given on Day 0 followed by a booster dose (placebo or 15 microg) on Day 84. Blood samples were taken before and 25 days after vaccination. There were four treatment groups: (i) 15 microg and placebo, (ii) 15 microg and 15 microg booster, (iii) 30 microg and placebo and (iv) 30 microg and 15 microg booster. Geometric mean antibody titers of those receiving the double vaccine dose was 15% (95% CI, 6% to 24%, P = 0.001) higher as compared to the standard 15 microg dose. A booster dose, given 84 days after the first vaccination, yielded postvaccination titters that were 14% (95% CI, 9% to 19%, P = 0.001) higher as compared to placebo. Subgroup analysis did not reveal patient groups that had a proportionally greater benefit from adapted vaccination strategies. It is concluded that higher antibody responses can be achieved in frail elderly people by a double vaccine dose or a booster vaccination.

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Improvement of the immunoglobulin subclass response to influenza vaccine in elderly nursing-home residents by the use of high-dose vaccines

Cited by 55 publications

References 26 publications

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

T cells and aging update February 1999

Randomized controlled trial of seroresponses to double dose and booster influenza vaccination in frail elderly subjects

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