Immune senescence and vaccines to prevent herpes zoster in older persons
Highlights
► Latent VZV is maintained in sensory neurons because of VZV-specific T-cell immunity. ► This immunity declines with age – the number/function of early effectors and effector memory. ► The loss of this T-cell immunity correlates with the occurrence of herpes zoster. ► A herpes zoster vaccine can restore this immunity and prevent herpes zoster. ► Suggestions are offered to improve the efficacy of zoster vaccine.
Section snippets
Background
Four vaccines are recommended for persons ≥60 years old [1]. In general their responses to these vaccines are significantly less robust than responses by younger vaccinees – in magnitude, duration, and quality of the response, and usually in terms of efficacy [2]. Thus, measuring vaccine-induced responses within this age group is an important technique for characterizing immune senescence and investigating mechanisms of age-related immune dysfunction. Such studies highlight the practical result
Varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI) prevents HZ
The basis for active immunization to prevent HZ is very different from that described for other vaccines recommended for older people. HZ represents reactivation of latent infection with VZV, which infects most individuals in childhood (as varicella) and persists life-long in neurons in ganglia of cranial nerves and the peripheral sensory nervous system [7, 8]. Extensive and definitive immunologic and clinical evidence (patients with certain inborn immunologic defects or after iatrogenic immune
Efficacy endpoints
The currently licensed HZ vaccine contains live, attenuated VZV that induces both VZV-CMI (measured most often as CD4+ responses) and VZV-specific antibody. The rationale for developing this vaccine was that reversing the decline of VZV-CMI with immunization would protect against HZ [9, 25••]. The efficacy of this vaccine in preventing HZ was 51% in vaccinees ≥60 years old, and the effect of age on this protection is evident when efficacy is stratified by age (Table 1). However, this
Improving HZ vaccines
It is apparent that the zoster vaccine-induced responses in many vaccinees are insufficient. It is noteworthy that HZ, which is a strong immunizing event, appears to provide protection against a second attack of HZ for 5 years or less, indicating a problem with immune memory [35], and the follow-up studies (described above) confirm a significant waning zoster vaccine efficacy over a 5-year interval.
Even if we knew the essential age-related deficits for protection to HZ, it is unlikely that
Conclusions
Although empiric approaches are described that might enhance the protective effects of zoster vaccine, developing a more effective vaccine with longer duration of protection will require more information on immune correlates of protection. In this quest, the phenotype, proliferative capacity, and persistence of CD8+ memory cells should be evaluated after zoster vaccine administration, at different ages, as well as the extent of VZV-specific T-cell regulation in vaccinees.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
References (46)
- et al.
Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxooid and acellular pertussis vaccine (Boostrix): results of two randomized trials
Vaccine
(2012) - et al.
Short-lived immunity against pertussis, age-specific routes of transmission, and the utility of a teenage booster vaccine
Vaccine
(2012) - et al.
Efficacy and effectiveness of influenza vaccine in elderly people: a systematic review
Lancet
(2005) - et al.
Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants
N Engl J Med
(2002) - et al.
Immune response of elderly individuals four years after receiving a live attenuated varicella vaccine
J Infect Dis
(1994) - et al.
Diabetes as a risk factor for herpes zoster infection: results of a population-based study in Israel
Infection
(2008) - et al.
Intradermal vaccine delivery: will new delivery systems transform vaccine administration?
Vaccine
(2008) - et al.
Interleukin (IL)-10, IL-12, and interferon-γ production in primary and memory immune responses to varicella-zoster virus
J Infect Dis
(1998) - ...
- et al.
Biology of immune responses to vaccines in elderly persons
Clin Infect Dis
(2008)
Protective Effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study
Clin Infect Dis
Varicella-zoster virus human ganglionic latency: a current summary
J Neurovirol
Zoster vaccine: current status and future prospects
Clin Infect Dis
VZV T cell-mediated immunity
Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia
Proc Natl Acad Sci USA
Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation
J Infect Dis
Clinical and subclinical reactivations of varicella zoster virus in immunocompromised patients
J Infect Dis
The nature of herpes zoster: a long-term study and a new hypothesis
Proc R Soc Med
Influence of age and nature of primary infection on varicella-zoster virus-specific cell-mediated immune responses
J Infect Dis
Selective decline in cellular immune response to varicella-zoster in the elderly
Neurology
Immune response to varicella-zoster in the aged
Arch Intern Med
Measurement of varicella-zoster virus (VZV)-specific cell-mediated immunity: comparison between VZV skin test and interferon-γ enzyme-linked immunospot assay
J Infect Dis
Cited by (85)
Incidence of complications of herpes zoster in individuals on immunosuppressive therapy: A register-based population study
2022, Journal of InfectionCitation Excerpt :Other complications such as cutaneous dissemination, encephalitis or life-threatening visceral involvement can also occur 12-14. HZ incidence in industrialized countries is estimated around 1.4 to 4.8/1000 person-year 8,15-20. It increases with age, reaching up to 10.0/1000 in people over 50 years of age 8,15,17-23.
The impact of ageing on monocytes and macrophages
2021, Immunology LettersThe aging immune system: Dysregulation, compensatory mechanisms, and prospects for intervention
2021, Handbook of the Biology of AgingImmune response and allergies to vaccines
2020, Revista Medica Clinica Las CondesEnhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase–induced inflammation
2018, Journal of Allergy and Clinical Immunology