Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

Abstract

Infectious diseases are a major cause for morbidity and mortality in the older population. Demographic changes will lead to increasing numbers of older persons over the next decades. Prevention of infections becomes increasingly important to ensure healthy aging for the individual, and to alleviate the socioeconomic burden for societies. Undoubtedly, vaccines are the most efficient health care measure to prevent infections. Age-associated changes of the immune system are responsible for decreased immunogenicity and clinical efficacy of most currently used vaccines in older age. Efficacy of standard influenza vaccines is only 30-50% in the older population. Several approaches, such as higher antigen dose, use of MF59 as adjuvant and intradermal administration have been implemented in order to specifically target the aged immune system. The use of a 23-valent polysaccharide vaccine against Streptococcus pneumoniae has been amended by a 13-valent conjugated pneumococcal vaccine originally developed for young children several years ago to overcome at least some of the limitations of the T cell-independent polysaccharide antigens, but still is only approximately 50% protective against pneumonia. A liveattenuated vaccine against herpes zoster, which has been available for several years, demonstrated efficacy of 51% against herpes zoster and 67% against post-herpetic neuralgia. Protection was lower in the very old and decreased several years after vaccination. Recently, a recombinant vaccine containing the viral glycoprotein gE and the novel adjuvant AS01B has been licensed. Phase III studies demonstrated efficacy against herpes zoster of approx. 90% even in the oldest age groups after administration of two doses and many countries now recommend the preferential use of this vaccine. There are still many infectious diseases causing substantial morbidity in the older population, for which no vaccines are available so far. Extensive research is ongoing to develop vaccines against novel targets with several vaccine candidates already being clinically tested, which have the potential to substantially reduce health care costs and to save many lives. In addition to the development of novel and improved vaccines, which specifically target the aged immune system, it is also important to improve uptake of the existing vaccines in order to protect the vulnerable, older population.

Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly

“…Despite being able to mitigate the severity of the disease to some degree, these vaccines often fail to induce protective immunity in the elderly. Several approaches are currently in place to improve vaccine effectiveness in this population [discussed in detail elsewhere (4)] and largely focus on the use of adjuvants, higher antigen doses and alternative routes of immunization.…”

“…Four vaccines are currently recommended for individuals over 65 years of age to protect against infections that disproportionately affect older adults, including influenza, herpes zoster, pneumococcal disease and tetanus and diphtheria. However, responses to these vaccines are often impaired in older individuals placing them at further risk of disease (3,4). This has considerable implications for vaccination against emerging infectious diseases such as COVID-19 that have a disproportionately larger effect on older subjects (5).…”

Identification and characterization of CD4+ T cell epitopes after Shingrix vaccination

“…The host immune system controls, but does not eliminate, the virus, as VZV enters a life-long latency state in the sensory neurons of the trigeminal and dorsal root ganglia (10). Usually later in life, the second disease state, Herpes Zoster (HZ) can manifest as a reactivation of latent virus that spreads throughout many neurons and along entire ganglia (10,32,52). Post-herpetic neuralgia (PHN) is a very common neurological complication of HZ and can persist for years.…”

Immunosenescence is both functional/adaptive and dysfunctional/maladaptive

“…As we have already stated, this is not the fault of the immune changes with aging but the use of inadequate vaccines, such as in the case of the influenza vaccines, and in particular vaccines that were designed for the immune systems of younger individuals. The increased success of the quadrivalent vaccine is the proof that elderly can built efficient and protective responses [232][233][234].…”