Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly

https://doi.org/10.1016/S0531-5565(01)00210-8Get rights and content

Abstract

While influenza immunization significantly reduces the risk of pneumonia and associated deaths, vaccination of elderly only affords 30–50% protection against influenza disease. The purpose of this study was to: (1) evaluate the consistency of immune responses across multiple years in young and elderly; (2) determine the contribution of antibody and cell-mediated responses in protection after immunization with influenza vaccine. Independently living healthy elderly (>200/year; mean age 78.8–80.6/year) were recruited yearly in this four year study. The results clearly demonstrate: (1) both young and elderly consistently produced significant antibody and T cell proliferative responses to influenza vaccine upon yearly immunization; however, both responses of elderly were significantly and consistently lower than young. (2) Percentages of both young and elderly demonstrating protective titers (i.e. HI≥40) increased post-immunization each year, but were consistently higher in young compared to elderly. (3) The risk of developing influenza disease after immunization was highest among elderly demonstrating neither antibody nor cell-mediated responses. Importantly, the risk of influenza disease was comparable in elderly demonstrating a cell-mediated response alone, an antibody response alone, or both cell-mediated and antibody responses. This suggests that cell-mediated responses play a significant role in protection in at least a subset of elderly from influenza disease after immunization.

Introduction

The morbidity and mortality associated with influenza disease is greatly increased in the elderly population. In fact, most of the deaths associated with secondary bacterial infections after influenza disease are predominantly in this segment of the population (Anonymous, 1998, Anonymous, 1999). Although immunization greatly reduces the risk of hospitalization and pneumonia associated with ‘influenza’, unfortunately, its effectiveness in preventing influenza disease is only 35–50% in the elderly (Govaert et al., 1994, Brandiss et al., 1981, Gross et al., 1989). Numerous studies have indicated that the elderly demonstrate decreased antibody production after influenza immunization (Keren et al., 1988, Beyer et al., 1989, Bernstein et al., 1999). However, it has also been reported that elderly demonstrating anti-influenza antibody (HI) titers after immunization that are generally considered to be protective (i.e. HI≥40), are still susceptible to influenza disease. In a study of 400 vaccinated elderly, 72 individuals developed laboratory confirmed influenza; of these individuals, 60% with influenza disease had post-immunization antibody titers ≥40 and 31% had titers ≥640 (Gravenstein et al., 1994). Although the general paradigm associated with effective viral vaccines is the development of sufficient levels of antibody to bind and neutralize the virus thus preventing infection, the lack of protection in the presence of high titers of appropriate antibody suggests that a cell-mediated immune response may be needed to afford protection after vaccination in the elderly.

The current study was performed to assess the role of both antibody and cell-mediated immunity in protection against influenza after immunization. The study confirms previous reports that after influenza immunization both antibody and cell-mediated responses of elderly are significantly decreased compared to young. In addition, the data suggest that either an antibody or a cell-mediated response can result in similar protection of the elderly after influenza immunization.

Section snippets

Subjects

Elderly subjects, ranging from 67 to 95 years of age, living independently at six local continuing care retirement communities (CCRCs) were included in this study. Young subjects, ranging from 22 to 39 years of age, were students and staff of MCP Hahnemann University. Table 1 shows the age and gender distributions of subjects. Age, gender, ethnicity, education, and economic status were similar among subjects from each of the CCRCs. Subjects were not taking medications that altered immune

Study design

The study was conducted over four years (1993–1996). As illustrated in Table 1, over 200 elderly were recruited each year of the four-year study. The mean age and gender distribution of the subjects across the four years was fairly constant. In years 2–4 of the study, a cohort of young subjects was also recruited. The number of young subjects was smaller than the number of elderly because our previous studies indicated that young individuals demonstrate considerably less heterogeneity in immune

Discussions

It is recognized by both geriatricians and epidemiologists, that influenza disease represents a significant risk to individuals ≥65 years of age. While influenza vaccination significantly reduces the risk of pneumonias and associated deaths in this population, there is still concern that the influenza vaccine does not have a greater protective effect against influenza disease itself. Multiple efforts are currently ongoing to develop a more effective influenza vaccine for the elderly. However,

Acknowledgements

We are indebted to the residents and staff of the participating CCRCs: Rydal Park, Cathedral Village, Medford Leas, Foulkeways at Gwynedd, Pennswood Village and Stapely Hall of Germantown. We thank Caroline Fidew for her data base management assistance and Marion Dorfman for excellent technical assistance. Supported by National Institutes of Health Grant NIH AG03934.

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