Berger, Rosemarie

Just, Max

Luescher, Doris

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THE JOURNAL OF INFECTIOUS DISEASES • VOL. 149, NO.4· APRIL 1984© 1984 by The University of Chicago. All rights reserved. 0022-1899/84/4904-0027$01.00Enhancement of Varicella-Zoster-Specific Immune Responses in the Elderly byBoosting with Varicella VaccineLegend. Varicella-zoster virus (VZV)-specific cell-me-diated immunity in 33 adult volunteers (age range, 55-65years) before and two months after inoculation with liveVZV vaccine. The subjects, who had previously beenscreened for a negative proliferative immune response toVZV antigen in an in vitro serum assay, were vaccinatedwith aKA-strain VZV vaccine (2,700 pfu; SmithKline-RIT, Rixensart, Belgium). Blood sampling was done onthe day of vaccination and two months later. Lympho-cytes were isolated by Ficoll-Hypaque separation. Cells(5 x 105)were cultivated in the presence of VZV antigen(sonicated VZV-infected MA 184 human foreskin fibro-blasts) or control antigen (sonicated uninfected fibro-blasts) after five and six days. 125I-iododeoxiuridine(1.25 J.lCi) and fluorodeoxiuridine (l0-6M) were added.After 18 hr the cells were harvested on paper disks,and the tracer incorporation was counted in a gammacounter. The geometric mean of three determinationswas used for the calculation of the specific increase (cpmof VZV - cpm of control) and the stimulation index(SI; cpm of VZV/cmp of control). Cell-mediated im-mune responses with a specific increase of 2,500 cpm andan SI of <3 were considered negative (.), those with aspecific increase of 2,500-6,000 and an SI of 3-5 wereconsidered weakly positive (0), and those with a specificincrease >6,000 and an SI of >5 were considered positive(0). Humoral antibodies to VZV were determined byELISA (Varicella Enzygnost'", Behring, Marburg, WestGermany).SI~ 2117127)(W5!C~IZ0~3-oJ::>~l-(/)2o••••••••••••••••••••••• ••• •••• •••before000oo000o 000800o00(i/~0o 000 00••• ••after647SummaryDuring the evaluation of specific immune responses toVZV in healthy elderly people, we observed an impair-ment of the lymphocyte transformation by VZV antigenin vitro despite normal values for the cell-mediatedimmune response to mitogens [1]. Our results were con-firmed by Burke et al [2], who also reported reducedskin-test reactivity to VZV antigen in older age groups.Approximately 20010 of 55- to 65-year-old healthy peoplewith a confirmed history of chickenpox and humoralantibodies to VZV show a negative lymphoproliferativeimmune response to VZV antigen. The possibility of acorrelation between this observation and the fact thatshortly after the appearance of clinical symptoms inherpes-zoster infections the cell-mediated immune re-sponse to VZV virus is also negative [3] remains to beestablished; nevertheless, with a view to the possibleprevention of herpes-zoster, we vaccinated 33 volunteershaving a reduced lymphoproliferative immune responseto VZV with live aKA-strain VZV vaccine. In 28 (85%)of the volunteers the vaccination induced a change froma negative to a positive cell-mediated immune responseto VZV antigen in vitro; we do not yet know why nostimulation was observed in the other five (15%), but wehope to be able to present some explanations by testingthe function of the suppressor/helper cells and theplasma factors. In all subjects humoral antibodies toVZV were present prior to administration of the boostervaccination. An increase in antibody titer was observedin >50070 of our vaccinees, suggesting at least some VZVreplication, despite preexisting humoral antibodies. Re-testing of a few of our volunteers one year after vaccina-tion showed that the boosting effect remained. The mostimportant question remaining to be answered - whethersuch an improvement in the lymphoproliferative im-mune response to VZV does in fact give protectionagainst herpes-zoster infection - can only be answeredby the clinical evaluation of a large number of vaccineesover a period of several years.ROSEMARIE BERGER, DORIS LUESCHER, MAX JUSTDepartment of Microbiology and Immunology,University Children's Hospital, Basel, SwitzerlandReferences1. Berger R, Florent G, Just M. Decrease of the lymphopro-liferative response to varicella-zoster virus antigen in theaged. Infect Immun 1981;32:24-72. Burke BL, Steele RW, Beard OW, Wood JS, Cain TO,Marmer OJ. Immune responses to varicella-zoster in theaged. Arch Intern Med 1982;142:291-33. Sorenson OS, Haahr S, Moller-Larsen A, Wildenhoff K.Cell-mediated and humoral immunity to herpesvirusesduring and after herpes zoster infections. Infect Immun1980; 29:369-75

Enhancement of Varicella-Zoster-Specific Immune Responses in the Elderly by Boosting with Varicella Vaccine

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