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  • 1969;43;264PediatricsPhilip Fireman, Gilbert Friday and Jesus Kumate

    EFFECT OF MEASLES VACCINE ON IMMUNOLOGIC RESPONSIVENESS

    http://pediatrics.aappublications.org/content/43/2/264the World Wide Web at:

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    ISSN: 0031-4005. Online ISSN: 1098-4275.PrintIllinois, 60007. Copyright 1969 by the American Academy of Pediatrics. All rights reserved.

    by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,

    at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from

  • 1969;43;264PediatricsPhilip Fireman, Gilbert Friday and Jesus Kumate

    EFFECT OF MEASLES VACCINE ON IMMUNOLOGIC RESPONSIVENESS

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    Online ISSN: 1098-4275.Copyright 1969 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it

    at Indonesia:AAP Sponsored on October 3, 2013pediatrics.aappublications.orgDownloaded from

  • (Received June 3, 1968; revision accepted for publication August 20, 1968.)Supported by Grants HD-02662 and FR-05507 from the National Institutes of Health, U.S. Public

    Health Service.P.F. is recipient of Research Career Development Award, HD-18,243, National Institutes of Health,

    U.S. Public Health Service.ADDRESS: (P.F.) Childrens Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213.

    PEDIATRICS, Vol. 43, No. 2, February 1969

    264

    EFFECT OF MEASLES VACCINE ONIMMUNOLOGIC RESPONSIVENESS

    Philip Fireman, M.D., Gilbert Friday, M.D., and Jesus Kumate, M.D.Department of Pediatrics, University of Pittsburgh School of Medicine, Childrens Hospital

    of Pittsburgh and Hospital Infantil de Mexico, Mexico City

    ABSTRACT. Immunologic responses, both humoraland cellular, following vaccination with live atten-uated measles vaccine were studied in 11 childrenand compared to the immunologic responses ob-served following vaccination with killed attenuatedmeasles virus and placebo. The attenuated measlesvirus temporarily suppressed the cutaneous delayedhypersensitivity reaction to purified protein deriva-tive for 1 to 4 weeks; in addition, the delayedhypersensitivity reactions to candida, vaccinia,diphtheria toxoid, poison ivy, and 2,4-dinitro-chlorobenzene antigens were also temporarilysuppressed for 1 to 4 weeks. A modest de-pression of total leucocyte counts, includingsmall lymphocytes, was noted for 1 to 3 weeks; atthe same time, the capacity of lymphocytes frompatients who received live measles vaccine to re-spond in vitro to stimulation with purified proteinderivative, candida, and ragweed antigens was

    suppressed without decrease in their in vitro re-sponse to phytohemagglutinin. Administration oflive measles vaccine did not decrease pre-existinghumoral antibody titers to diphtheria toxoid or po-liovirus, serum yG-, yA- and yM-globulin concen-trations or immediate wheal and flare hypersensitiv-ity skin reactions. The mechanism of the suppressionof delayed hypersensitivity by live measles vaccineappears dependent on a viable virus since killedmeasles vaccine had no demonstrable effect onpre-existing cutaneous delayed hypersensitivity oron the in vitro lymphocyte responses. This studydemonstrates that live attenuated measles virus in-terferes with the capacity of the recipient to ex-press cutaneous delayed hypersensitivity withoutsuppression of humoral antibody. Pediatrics,43:264, 1969, si.ss vccnir, rMMuNo-suP-PRESSION, HYPERSENSITIVITY-DELAYED vAccINA-

    TION-MEASLES.

    T HE temporary suppression of cutaneousdelayed hypersensitivity to tuberculin

    in man by measles virus, both natural andattenuated, has been reported by several in-vestigators.T The mechanism of this ob-served decrease in skin reactivity to tuber-culin has not been elucidated. It is also notknown if the measles virus affects any otherparameters of the human hosts immunologicresponse. The use of measles vaccine in thegeneral pediatric population has providedan opportunity to study in detail both hu-moral and cellular immunologic responsive-ness of the human host during a syndromewhich resembles a mild case of naturallyacquired measles in which the date of in-fection is known and alterations of symp-toms, physical findings, and laboratory re-

    suits can be accurately recorded. The re-suits of this study show that the administra-lion of live attenuated measles virus inter-fered with the capacity of the recipients toexpress cutaneous delayed hypersensitivitywithout suppression of humoral antibody.In addition, the capacity of peripheral lym-phocytes from patients who received livemeasles vaccine to respond to antigenicstimulation in vitro was suppressed.

    Patients

    MATERIALS AND METHODS

    The children selected to receive live at-tenuated measles vaccine were followed inthe outpatient allergy clinics of ChildrensHospital of Pittsburgh. Their ages ranged

  • ARTICLES 265

    from 5 to 16 years. Two of the patientswere receiving isoniazid therapy because ofrecent conversion from a negative tuberculinskin test to a positive tuberculin skin test.Three of the patients studied had a priorclinical history of measles, confirmed by se-rologic examination. As a comparisongroup, five other children received formalde-hyde inactivated measles virus, and five ad-ditional children were given as a placebo 0.5ml of the diluent used to reconstitute theattenuated live measles virus. The prevac-cine data were obtained at least 1 weekprior to administration of the measles vac-clues or placebo.

    Measles VaccinesThe reconstituted lyophilized live vac-

    cine was given subcutaneously in a vol-ume of 0.5 ml which contained at least 1,000TCID5O of attenuated measles virus pre-pared from the Edinonston strain. The forrnmaldehyde inactivated, alum precipitatedrubeola virus, which was also derived fromthe Edmonston strain, was administered in-tramuscularly in a volume of 0.5 ml. Nogamma-globulin was given with eitherthe live attenuated or inactivated measlesvaccines.

    Bacill. Calmeff. GurIn (BCG)*Each recipient received 0.1 ml of viable

    BCG intracutaneously in the deltoid region.

    Skin TestsDelayed hypersensitivity skin tests were

    read at 24 and 48 hours after challengewith appropriate antigen. Skin tests of lessthan 5 mm of erythema and induration wereinterpreted as negative. Immediate hyper-sensitivity skin tests were read at 15 and 20minutes after challenge with appropriateantigen. Skin tests which exhibited lessthan 5 mm of wheal and erythema wereinterpreted as negative. All skin tests weremeasured by two observers, one of whomwas not aware of the protocoL

    . Kindly provided by the Allegheny CountyHealth Department, Pittsburgh, Pennsylvania.

    Skin Test Antigens

    Purified protein derivative (PPD),$ 0.1iLg, was administered intradermally in a vol-ume of 0.1 ml and, if no skin reactivity waselicited after 48 hours, then 5 tg was ad-ministered intradermally in a volume of 0.1ml. Candida antigen was given intrader-mally in a concentration of 1/1,000 and, ifno reactivity developed, then 1/100 dilutionin 0.1 ml was given intradermally. Vacciniavaccine was heated for 1 hour at 60#{176}Cpriorto use as an intradermal skin test antigen.Diphtheria toxoid diluted 1/10 was appliedintradermally in a volume of 0.1 ml and, ifno delayed hypersensitivity was elicited,then 0.1 ml of a 1/1 dilution was given in-tradermally A contact dermal sensitizer of2,4.dinitrochlorobenzene diluted 1/100 incorn oil was applied; 10 days later, thesensitized patients were challenged bypatch testing with 1/1,000 dilution of2,4-dinitrochlorobenzene. Poison ivy anti-gen was applied topically as a patch test.House dust, ragweed, and egg skin test an-tigens were applied intradermally in a volume of 0.02 ml and examined at 15 and 20minutes.

    Leucocyte Cultures

    Human peripheral leucocytes were iso-