Immunity to influenza in the elderly

doi:10.1016/S0264-410X(99)00507-1

Vaccine

Volume 18, Issue 16, 25 February 2000, Pages 1686-1689

https://doi.org/10.1016/S0264-410X(99)00507-1 Get rights and content

Abstract

Influenza is caused by a constantly varying segmented RNA virus that necessitates yearly review of vaccine composition. Humans over the age of 65 years are considered at high risk from influenza; during influenza epidemics the rate of hospitalization in the elderly is very high and up to 90% mortality can occur. Vaccination of the elderly has been shown to be efficacious and cost effective but immunological senescence in the institutionally confined frail elderly is demonstrated by failure to induce herd immunity after vaccination. Reductions in B- and T-cell immunity and in levels of interleukin-2 are age related. Attempts to increase the immunoresponsiveness of the elderly to influenza vaccines have given mixed results. The most convincing evidence is in rodents where dietary caloric restriction has been shown to enhance viral immunity.

Introduction

Influenza viruses continue to evolve, and new antigenic variants (drift strains) emerge constantly, giving rise to yearly epidemics. In addition, strains to which most humans have no immunity appear suddenly, and the resulting pandemics vary from serious to catastrophic. Influenza viruses are unique among respiratory tract viruses in that they undergo continuous genetic variation. Both surface antigens of the influenza A viruses undergo two types of variation: drift and shift [1] whereas influenza B viruses show only antigenic drift. Antigenic drift involves minor changes in the hemagglutinin (HA) and neuraminidase (NA), whereas antigenic shift involves major changes in these molecules resulting from replacement of the gene segment.

Section snippets

Variation: antigenic drift and shift

After the appearance of a new subtype, antigenic differences between isolates can be detected using ferret antisera for analysis. Analysis with monoclonal antibodies indicates that major antigenic heterogeneity is detectable among different influenza virus isolates at anytime [2]. Antigenic drift occurs by accumulation of a series of point mutations resulting in amino acid substitutions in antigenic sites A to E at the membrane distal region of the HA. These substitutions prevent binding of

Prevention and control of influenza

Two options are available for the control of influenza A virus: vaccination or therapy with influenza specific antiviral agents. With increased global surveillance by the World Health Organization, vaccines and epidemic strains are usually well matched and effective at providing protection against influenza A and B.

The available vaccines include purified inactivated egg-grown whole virus or purified surface antigens. Only surface antigens (subvirion vaccines) are recommended for children under

Immune response

Recovery from influenza viral infection involves both humoral and cell-mediated responses. The surface glycoproteins are of the most importance in the humoral response, and internal proteins predominate in the cellular response. Mucosal [immunoglobulin (Ig)A] and serum (IgG) antibodies to the HA molecule neutralize viral infectivity and are primarily responsible for resistance to infection. This is the basis of vaccination against current epidemic strains with killed virus. The Ig response to

Influenza in the elderly

Elderly people over the age of 65 years are considered to be the highest risk group for influenza and yearly vaccination is recommended [6], [7]. A typical influenza A epidemic in the United States can be associated with hundreds of thousands of excess hospitalizations, mainly in persons over 65 with up to 90% excess deaths in this age group [8]. The questions that arise are whether influenza vaccination is efficacious and cost effective in the elderly or whether immunological senescence

Immunological senescence

Replicative senescence is a characteristic of all normal somatic cells that undergo a finite number of cell divisions in tissue culture reaching an irreversible state of growth arrest — the so-called Hayflick limit [15]. The identification of replicative senescence in vivo, especially in lymphocytes from the elderly and decline in T-cells lacking CD28 [16] has led to the realization that the immune system has finite proliferative potential [17]. Studies in humans and mice have demonstrated

Acknowledgements

These studies were supported by Public Health Research Grants A129680 and AI95357 and Cancer Support (CORE) grant CA-21765 from the National Institutes of Health and by the American Lebanese Syrian Associated Charities. We thank Alice Herren for preparation of the manuscript.

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Immunity to influenza in the elderly

Abstract

Introduction

Section snippets

Variation: antigenic drift and shift

Prevention and control of influenza

Immune response

Influenza in the elderly

Immunological senescence

Acknowledgements

Lancet

Exp. Cell. Res.

Exp. Gerontol.

Immunol. Today

Cell Immunol

Vaccine

Exp. Gerontol.

Vaccine

Mech. Age. Dev.

Orthomyxoviruses

Antigenic and amino acid sequence analysis of the variants of H1N1 influenza virus in 1986

Bull. World Health Organ.

Evolutionary changes in influenza B are not primarily governed by antibody selection

Proc. Natl. Acad. Sci. USA

Initial genetic characterization of the 1918 ‘Spanish’ influenza virus

Science

Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene

Proc. Natl. Acad. Sci. USA

Influenza: its control in persons and populations

J. Infect. Dis.

Influenza vaccination for all elderly

Gerontology

Impact of epidemic type A influenza in a defined adult population

Am. J. Epid.

The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community

N. Engl. J. Med.

The efficacy of influenza vaccination in elderly individuals: a randomized double-blind placebo-controlled trial

JAMA