Immune senescence in old and very old rhesus monkeys: reduced antibody response to influenza vaccination

Coe, Christopher L.; Lubach, Gabriele R.; Kinnard, Jeanne

doi:10.1007/s11357-011-9356-8

Cited by 28 publications

(18 citation statements)

References 36 publications

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“…In animal models of aging and vaccination, it has also been shown that a dual immunization regimen could offer an alternative approach for enhancing antibody response to influenza vaccine in the aged host. 47 Given that old age can also differentially affect the synthesis of the four primary IgG subsets, it is possible that we might have detected more of an influence of the interventions if we had assayed each IgG subset individually. 48 The antibody responses of this community sample of older adults, which included many overweight individuals, also did not confirm recently reported associations between a high BMI and peak influenza antibody concentrations.…”

Section: Discussionmentioning

confidence: 99%

Age and psychological influences on immune responses to trivalent inactivated influenza vaccine in the meditation or exercise for preventing acute respiratory infection (MEPARI) trial

Hayney

Coe

Müller

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Discussionmentioning

confidence: 99%

Age and psychological influences on immune responses to trivalent inactivated influenza vaccine in the meditation or exercise for preventing acute respiratory infection (MEPARI) trial

Hayney

Coe

Müller

et al. 2013

Human Vaccines & Immunotherapeutics

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“…One mechanism concerns intrinsic drivers towards immunosenescence based on the ageing of the immune system, a complex process that is not yet fully understood, and may involve the age-dependent functioning of T-cells and a decreased output of naïve T-cells as a result of involution of the thymus [8–11]. Such an intrinsic immunosenescent process has been observed in studies of influenza-naïve rhesus macaques, where ageing results in declined antibody response to influenza vaccination [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

The confounded effects of age and exposure history in response to influenza vaccination

Höpping

McElhaney²,

Fonville

et al. 2016

Vaccine

100

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Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence – the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly.

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“…Almost all components of the immune system have been shown to undergo age-associated restructuring that greatly impacts immune function [2][3][4][5]. The decline in immune function with age also results in reduced vaccine efficacy, further enhancing susceptibility to infection in the elderly [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses

et al. 2014

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BackgroundMany respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure.ResultsSignificant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age.ConclusionsThis study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.

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Immune senescence in old and very old rhesus monkeys: reduced antibody response to influenza vaccination

Cited by 28 publications

References 36 publications

Age and psychological influences on immune responses to trivalent inactivated influenza vaccine in the meditation or exercise for preventing acute respiratory infection (MEPARI) trial

Age and psychological influences on immune responses to trivalent inactivated influenza vaccine in the meditation or exercise for preventing acute respiratory infection (MEPARI) trial

The confounded effects of age and exposure history in response to influenza vaccination

Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses

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