Immunosenescence and Novel Vaccination Strategies for the Elderly

Influenza vaccination of elderly individuals is recommended worldwide. Our aim was to review the evidence of efficacy and effectiveness of influenza vaccines in individuals aged 65 years or older. We searched five electronic databases to December, 2004, in any language, for randomised (n=5), cohort (n=49), and case-control (n=10) studies, assessing efficacy against influenza (reduction in laboratory-confirmed cases) or effectiveness against influenza-like illness (reduction in symptomatic cases). We expressed vaccine efficacy or effectiveness as a proportion, using the formula VE=1-relative risk (RR) or VE*=1-odds ratio (OR). We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications, and deaths. In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against influenza-like illness was 23% (95% CI 6-36) and non-significant against influenza (RR 1.04, 0.43-2.51). Well matched vaccines prevented pneumonia (VE 46%, 30-58) and hospital admission (VE 45%, 16-64) for and deaths from influenza or pneumonia (VE 42%, 17-59), and reduced all-cause mortality (VE 60%, 23-79). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19, 0.02-2.01), influenza-like illness (RR 1.05, 0.58-1.89), or pneumonia (RR 0.88, 0.64-1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%, 12-38) and all-cause mortality (VE 42%, 24-55). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%, 21-33), respiratory diseases (VE* 22%, 15-28), and cardiac disease (VE* 24%, 18-30), and for all-cause mortality (VE* 47%, 39-54). In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest.

Our improved understanding of how innate immune responses can be initiated and how they can shape adaptive B- and T-cell responses is having a significant impact on vaccine development by directing the development of defined adjuvants. Experience with first generation vaccines, as well as rapid advances in developing defined vaccines containing Toll-like receptor ligands (TLRLs), indicate that an expanded number of safe and effective vaccines containing such molecules will be available in the future. In this review, we outline current knowledge regarding TLRs, detailing the different cell types that express TLRs, the various signaling pathways TLRs utilize, and the currently known TLRLs. We then discuss the current status of TLRLs within vaccine development programs, including the importance of appropriate formulation, and how recent developments can be used to better define the mechanisms of action of vaccines. Finally, we introduce the possibility of using TLRLs, either in combination or with non-TLRLs, to synergistically potentiate vaccine-induced responses to provide not only prophylactic, but therapeutic protection against infectious diseases and cancer. © 2010 John Wiley & Sons A/S.

To quantify the protective efficacy of influenza vaccine in elderly persons. A MEDLINE search was done using the index terms influenza vaccine, vaccine efficacy, elderly, mortality, hospitalized, and pneumonia. Appropriate references in the initially selected articles were also reviewed. Only cohort observational studies with mortality assessment were included in the meta-analysis. In addition, 3 recent case-control studies, 2 cost-effectiveness studies, and 1 randomized, double-blind, placebo-controlled trial were reviewed. Vaccine and epidemic virus strains, age and sex of patients, severity of illness, patient status, and study design were recorded. Upper respiratory illness, hospitalization, pneumonia, and mortality were used as outcome measures. In a meta-analysis of 20 cohort studies, the pooled estimates of vaccine efficacy (1-odds ratio) were 56% (95% Cl, 39% to 68%) for preventing respiratory illness, 53% (Cl, 35% to 66%) for preventing pneumonia, 50% (Cl, 28% to 65%) for preventing hospitalization, and 68% (Cl, 56% to 76%) for preventing death. Vaccine efficacy in the case-control studies ranged from 32% to 45% for preventing hospitalization for pneumonia, from 31% to 65% for preventing hospital deaths from pneumonia and influenza, from 43% to 50% for preventing hospital deaths from all respiratory conditions, and from 27% to 30% for preventing deaths from all causes. The randomized, double-blind, placebo-controlled trial showed a 50% or greater reduction in influenza-related illness. Recent cost-effectiveness studies confirm the efficacy of influenza vaccine in reducing influenza-related morbidity and mortality and show that vaccine provides important cost savings per year per vaccinated person. Despite the paucity of randomized trials, many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain. Influenza immunization is an indispensable part of the care of persons 65 years of age and older. Annual vaccine administration requires the attention of all physicians and public health organizations.