Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers
Identifieur interne : 000104 ( Istex/Corpus ); précédent : 000103; suivant : 000105Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers
Auteurs : Robert F. Betts ; R. Gordon Douglas ; Hunien F. Maassab Jr. ; Dan C. Deborde ; Mary Lou Clements ; Brian R. MurphySource :
- Journal of Medical Virology [ 0146-6615 ] ; 1988-10.
English descriptors
- Teeft :
- Adult volunteers, Antibody response, Attenuated, Betts, Clements, Different doses, Donor virus, Dos, Dose response, Experimental challenge, Genes coding, Hemagglutinin, High rate, Immunity murphy, Infection frequency, Infectious diseases, Infectivity, Infectivity titer, Influenza, Influenza vaccine reactionicity, Influenza virus, Internal genes, Lower doses, Maassab, Nasal washes, Natural influenza, Reactogenicity, Reassortant, Reassortant vaccines, Reassortant virus, Recombinant, Recombinant virus, Symptom, Systemic complaints, Systemic symptoms, Undiluted vaccine, Vaccine, Vaccine administration, Vaccine development, Vaccine reactogenicity, Vaccine virus, Virus, Virus inoculum, Virus vaccine, Virus vaccines, Wild type, Young children.
Abstract
Live attenuated cold‐adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.
Url:
DOI: 10.1002/jmv.1890260209
Links to Exploration step
ISTEX:DA95D4B0A16E872B4AE7E2BAC0D1D75D870D0613Le document en format XML
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Gordon Douglas</name><affiliation><mods:affiliation>Infectious Disease Unit, University of Rochester, Rochester New York</mods:affiliation></affiliation><affiliation><mods:affiliation>Cornell Medical Center, The New York Hospital New York</mods:affiliation></affiliation></author><author><name sortKey="Maassab Jr, Hunien F" sort="Maassab Jr, Hunien F" uniqKey="Maassab Jr H" first="Hunien F." last="Maassab Jr.">Hunien F. Maassab Jr.</name><affiliation><mods:affiliation>University of Michigan</mods:affiliation></affiliation></author><author><name sortKey="Deborde, Dan C" sort="Deborde, Dan C" uniqKey="Deborde D" first="Dan C." last="Deborde">Dan C. 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Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. 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Betts</name><affiliations><json:string>Infectious Disease Unit, University of Rochester, Rochester New York</json:string><json:string>Correspondence address: Infectious Disease Unit, University of Rochester, Rochester, NY 14642===</json:string></affiliations></json:item><json:item><name>R. Gordon Douglas</name><affiliations><json:string>Infectious Disease Unit, University of Rochester, Rochester New York</json:string><json:string>Cornell Medical Center, The New York Hospital New York</json:string></affiliations></json:item><json:item><name>Hunien F. Maassab Jr.</name><affiliations><json:string>University of Michigan</json:string></affiliations></json:item><json:item><name>Dan C. Deborde</name><affiliations><json:string>University of Michigan</json:string></affiliations></json:item><json:item><name>Mary Lou Clements</name><affiliations><json:string>Center for Vaccine Development, University of Maryland</json:string></affiliations></json:item><json:item><name>Brian R. Murphy</name><affiliations><json:string>National Institutes of Allergy and Infectious Diseases, Influenza Laboratory</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>influenza</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>cold‐adapted vaccine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>vaccine reactogenicity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>live vaccine</value></json:item></subject><articleId><json:string>JMV1890260209</json:string></articleId><arkIstex>ark:/67375/WNG-MSPH10MV-Q</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Live attenuated cold‐adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.</abstract><qualityIndicators><score>7.9</score><pdfWordCount>3536</pdfWordCount><pdfCharCount>22809</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>504 x 719.759 pts</pdfPageSize><pdfWordsPerPage>393</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>197</abstractWordCount><abstractCharCount>1393</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers</title><pmid><json:string>3183640</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Medical Virology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1096-9071</json:string></doi><issn><json:string>0146-6615</json:string></issn><eissn><json:string>1096-9071</json:string></eissn><publisherId><json:string>JMV</json:string></publisherId><volume>26</volume><issue>2</issue><pages><first>175</first><last>183</last><total>9</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Article</value></json:item><json:item><value>Articles</value></json:item></subject></host><namedEntities><unitex><date><json:string>1988</json:string><json:string>1980</json:string></date><geogName></geogName><orgName><json:string>University of Michigan</json:string><json:string>University of Rochester</json:string><json:string>Cornell Medical Center</json:string><json:string>Hopkins University</json:string><json:string>New York Hospital New York</json:string><json:string>National Institute of Allergy and Infectious Diseases</json:string><json:string>National Institutes of Allergy and Infectious Diseases</json:string><json:string>Clinical Research Center</json:string><json:string>University of Maryland</json:string><json:string>Division of Research Resources</json:string><json:string>Liss, Inc.</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>I. Comparison</json:string><json:string>Alan Kendall</json:string><json:string>Robert F. Betts</json:string><json:string>F. Maassab</json:string><json:string>Gordon Douglas</json:string><json:string>Dan C. DeBorde</json:string><json:string>Ann Arbor</json:string><json:string>Mary Lou</json:string><json:string>Brian R. Murphy</json:string><json:string>Margaret Aldrich</json:string></persName><placeName><json:string>Rochester</json:string><json:string>NY</json:string><json:string>Korea</json:string><json:string>GA</json:string><json:string>Atlanta</json:string><json:string>Baltimore</json:string><json:string>MD</json:string><json:string>York</json:string><json:string>Reactionicity</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Clements et al., 19861</json:string><json:string>Murphy et al., 19791</json:string><json:string>Cate and Couch, 19821</json:string><json:string>Wright et al., 1982</json:string><json:string>Clements et al., 1984</json:string><json:string>Gorse et al., 1986</json:string><json:string>Hrabar et al., 19771</json:string><json:string>Johnson et al., 19851</json:string><json:string>Wright et al., 19821</json:string><json:string>King et al., 19871</json:string><json:string>VanVoris et al., 19851</json:string><json:string>Murphy et al., 1977</json:string><json:string>Clements et al., 1983</json:string><json:string>Clements et al., 19831</json:string><json:string>Kendal et al., 19811</json:string><json:string>Gorse et al.</json:string><json:string>Johnson et al., 1985</json:string><json:string>Kendall et al., 1981</json:string><json:string>Betts et al., 1985</json:string><json:string>Hrabar et al., 1977</json:string><json:string>Clements et al., 19841</json:string><json:string>Murphy et al., 1981</json:string><json:string>Clements et al., 1984a,b</json:string><json:string>King et al., 1987</json:string><json:string>Clements et al., 1984a</json:string><json:string>Lazar et al. , 1980</json:string><json:string>Belshe and VanVoris, 1984</json:string><json:string>Clements et al., 1986</json:string><json:string>Cate and Couch, 1982</json:string><json:string>Betts et al., 19851</json:string><json:string>Murphy et al., 1980</json:string><json:string>Nicholson et al., 19871</json:string><json:string>Davenport et al., 19771</json:string><json:string>Betts et al.</json:string><json:string>Cate and Couch 1982</json:string><json:string>Davenport et al., 1977</json:string><json:string>Betts et al. 19861</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-MSPH10MV-Q</json:string></ark><categories><wos><json:string>1 - 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Gordon</forename><surname>Douglas</surname></persName><affiliation><orgName type="laboratory">Infectious Disease Unit</orgName><orgName type="institution">University of Rochester</orgName><address><addrLine>Rochester New York</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation><affiliation><orgName type="institution">Cornell Medical Center</orgName><orgName type="institution">The New York Hospital New York</orgName></affiliation></author><author xml:id="author-0002"><persName><genName>Jr.</genName><forename type="first">Hunien F.</forename><surname>Maassab</surname></persName><affiliation><orgName type="institution">University of Michigan</orgName></affiliation></author><author xml:id="author-0003"><persName><forename type="first">Dan C.</forename><surname>Deborde</surname></persName><affiliation><orgName type="institution">University of Michigan</orgName></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Mary Lou</forename><surname>Clements</surname></persName><affiliation><orgName type="institution">Center for Vaccine Development</orgName><orgName type="institution">University of Maryland</orgName></affiliation></author><author xml:id="author-0005"><persName><forename type="first">Brian R.</forename><surname>Murphy</surname></persName><affiliation><orgName type="institution">National Institutes of Allergy and Infectious Diseases</orgName><orgName type="laboratory">Influenza Laboratory</orgName></affiliation></author><idno type="istex">DA95D4B0A16E872B4AE7E2BAC0D1D75D870D0613</idno><idno type="ark">ark:/67375/WNG-MSPH10MV-Q</idno><idno type="DOI">10.1002/jmv.1890260209</idno><idno type="unit">JMV1890260209</idno><idno type="toTypesetVersion">file:JMV.JMV1890260209.pdf</idno></analytic><monogr><title level="j" type="main">Journal of Medical Virology</title><title level="j" type="alt">JOURNAL OF MEDICAL VIROLOGY</title><idno type="pISSN">0146-6615</idno><idno type="eISSN">1096-9071</idno><idno type="book-DOI">10.1002/(ISSN)1096-9071</idno><idno type="book-part-DOI">10.1002/jmv.v26:2</idno><idno type="product">JMV</idno><imprint><biblScope unit="vol">26</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="175">175</biblScope><biblScope unit="page" to="183">183</biblScope><biblScope unit="page-count">9</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>New York</pubPlace><date type="published" when="1988-10"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef><appInfo><application ident="pub2tei" version="1.0.10" when="2019-12-20"><label>pub2TEI-ISTEX</label><desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>Live attenuated cold‐adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID<hi rend="subscript">50</hi>) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID<hi rend="subscript">50</hi>. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="kwd1">influenza</term><term xml:id="kwd2">cold‐adapted vaccine</term><term xml:id="kwd3">vaccine reactogenicity</term><term xml:id="kwd4">live vaccine</term></keywords><keywords rend="articleCategory"><term>Article</term></keywords><keywords rend="tocHeading1"><term>Articles</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-MSPH10MV-Q/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>New York</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1096-9071</doi><issn type="print">0146-6615</issn><issn type="electronic">1096-9071</issn><idGroup><id type="product" value="JMV"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="JOURNAL OF MEDICAL VIROLOGY">Journal of Medical Virology</title><title type="short">J. 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Virol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="20"><doi origin="wiley" registered="yes">10.1002/jmv.v26:2</doi><numberingGroup><numbering type="journalVolume" number="26">26</numbering><numbering type="journalIssue">2</numbering></numberingGroup><coverDate startDate="1988-10">October 1988</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="9" status="forIssue"><doi origin="wiley" registered="yes">10.1002/jmv.1890260209</doi><idGroup><id type="unit" value="JMV1890260209"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Article</title><title type="tocHeading1">Articles</title></titleGroup><copyright ownership="publisher">Copyright © 1988 Wiley‐Liss, Inc., A Wiley Company</copyright><eventGroup><event type="manuscriptAccepted" date="1988-04-21"></event><event type="firstOnline" date="2005-12-09"></event><event type="publishedOnlineFinalForm" date="2005-12-09"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-15"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-20"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-30"></event></eventGroup><numberingGroup><numbering type="pageFirst">175</numbering><numbering type="pageLast">183</numbering></numberingGroup><correspondenceTo>Infectious Disease Unit, University of Rochester, Rochester, NY 14642===</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JMV.JMV1890260209.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="23"></count></countGroup><titleGroup><title type="main" xml:lang="en">Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers</title><title type="short" xml:lang="en">Live Influenza Vaccine Reactionicity</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><honorifics>Dr.</honorifics><givenNames>Robert F.</givenNames><familyName>Betts</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>R. Gordon</givenNames><familyName>Douglas</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Hunien F.</givenNames><familyName>Maassab</familyName><nameSuffix>Jr.</nameSuffix></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Dan C.</givenNames><familyName>Deborde</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Mary Lou</givenNames><familyName>Clements</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Brian R.</givenNames><familyName>Murphy</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Infectious Disease Unit, University of Rochester, Rochester New York</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Cornell Medical Center, The New York Hospital New York</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>University of Michigan</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Center for Vaccine Development, University of Maryland</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>National Institutes of Allergy and Infectious Diseases, Influenza Laboratory</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">influenza</keyword><keyword xml:id="kwd2">cold‐adapted vaccine</keyword><keyword xml:id="kwd3">vaccine reactogenicity</keyword><keyword xml:id="kwd4">live vaccine</keyword></keywordGroup><fundingInfo><fundingAgency>Public Health Service</fundingAgency><fundingNumber>NO1‐AI‐12666</fundingNumber><fundingNumber>NO1‐AI‐02653</fundingNumber><fundingNumber>NO1‐AI‐72521</fundingNumber></fundingInfo><fundingInfo><fundingAgency>National Institute of Allergy and Infectious Diseases</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Public Health Service</fundingAgency><fundingNumber>RR00044</fundingNumber><fundingNumber>RR00644</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Division of Research Resources</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institutues of Health</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Live attenuated cold‐adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID<sub>50</sub>) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID<sub>50</sub>. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Live Influenza Vaccine Reactionicity</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers</title></titleInfo><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="given">Robert F.</namePart><namePart type="family">Betts</namePart><affiliation>Infectious Disease Unit, University of Rochester, Rochester New York</affiliation><affiliation>Correspondence address: Infectious Disease Unit, University of Rochester, Rochester, NY 14642===</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R. Gordon</namePart><namePart type="family">Douglas</namePart><affiliation>Infectious Disease Unit, University of Rochester, Rochester New York</affiliation><affiliation>Cornell Medical Center, The New York Hospital New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hunien F.</namePart><namePart type="family">Maassab Jr.</namePart><affiliation>University of Michigan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dan C.</namePart><namePart type="family">Deborde</namePart><affiliation>University of Michigan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mary Lou</namePart><namePart type="family">Clements</namePart><affiliation>Center for Vaccine Development, University of Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Brian R.</namePart><namePart type="family">Murphy</namePart><affiliation>National Institutes of Allergy and Infectious Diseases, Influenza Laboratory</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">1988-10</dateIssued><dateValid encoding="w3cdtf">1988-04-21</dateValid><copyrightDate encoding="w3cdtf">1988</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">0</extent><extent unit="tables">2</extent><extent unit="references">23</extent></physicalDescription><abstract lang="en">Live attenuated cold‐adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.</abstract><note type="funding">Public Health Service - No. NO1‐AI‐12666; No. NO1‐AI‐02653; No. NO1‐AI‐72521; </note><note type="funding">National Institute of Allergy and Infectious Diseases</note><note type="funding">Public Health Service - No. RR00044; No. RR00644; </note><note type="funding">Division of Research Resources</note><note type="funding">National Institutues of Health</note><subject lang="en"><genre>keywords</genre><topic>influenza</topic><topic>cold‐adapted vaccine</topic><topic>vaccine reactogenicity</topic><topic>live vaccine</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Virology</title></titleInfo><titleInfo type="abbreviated"><title>J. Med. Virol.</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>article-category</genre><topic>Article</topic><topic>Articles</topic></subject><identifier type="ISSN">0146-6615</identifier><identifier type="eISSN">1096-9071</identifier><identifier type="DOI">10.1002/(ISSN)1096-9071</identifier><identifier type="PublisherID">JMV</identifier><part><date>1988</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>175</start><end>183</end><total>9</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit1"><titleInfo><title>Cold recombinant influenza A/California/10/78 (H1N1) virus vaccine (CR37) in seronegative children: Infectivity and efficacy against investigational challenge</title></titleInfo><name type="personal"><namePart type="given">RB</namePart><namePart type="family">Belshe</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">LP</namePart><namePart type="family">VanVoris</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Belshe RB, VanVoris LP (1984): Cold recombinant influenza A/California/10/78 (H1N1) virus vaccine (CR37) in seronegative children: Infectivity and efficacy against investigational challenge. Journal of Infectious Diseases 149: 735–740.</note><part><date>1984</date><detail type="volume"><caption>vol.</caption><number>149</number></detail><extent unit="pages"><start>735</start><end>740</end></extent></part><relatedItem type="host"><titleInfo><title>Journal of Infectious Diseases</title></titleInfo><part><date>1984</date><detail type="volume"><caption>vol.</caption><number>149</number></detail><extent unit="pages"><start>735</start><end>740</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit2"><titleInfo><title>Resistance to challenge with influenza A/Hong Kong 123/77 (H1N1) wild type virus induced by live attenuated A/Hong Kong 123/77 (H1N1) cold adapted reassortant virus</title></titleInfo><name type="personal"><namePart type="given">RF</namePart><namePart type="family">Betts</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">RG</namePart><namePart type="family">Douglas Jr</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BR</namePart><namePart type="family">Murphy</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Betts RF, Douglas RG Jr, Murphy BR (1985): Resistance to challenge with influenza A/Hong Kong 123/77 (H1N1) wild type virus induced by live attenuated A/Hong Kong 123/77 (H1N1) cold adapted reassortant virus. Journal of Infectious Diseases 151: 744–745.</note><part><date>1985</date><detail type="volume"><caption>vol.</caption><number>151</number></detail><extent unit="pages"><start>744</start><end>745</end></extent></part><relatedItem type="host"><titleInfo><title>Journal of Infectious Diseases</title></titleInfo><part><date>1985</date><detail type="volume"><caption>vol.</caption><number>151</number></detail><extent unit="pages"><start>744</start><end>745</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit3"><titleInfo><title>Live influenza A/Victoria/75 (H3N2) virus vaccine: Reactogenicity, immunogenicity and protection against wild type virus challenge</title></titleInfo><name type="personal"><namePart type="given">TR</namePart><namePart type="family">Cate</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">RB</namePart><namePart type="family">Couch</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Cate TR, Couch RB (1982): Live influenza A/Victoria/75 (H3N2) virus vaccine: Reactogenicity, immunogenicity and protection against wild type virus challenge. Infection and Immunity 38: 141–146.</note><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>38</number></detail><extent unit="pages"><start>141</start><end>146</end></extent></part><relatedItem type="host"><titleInfo><title>Infection and Immunity</title></titleInfo><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>38</number></detail><extent unit="pages"><start>141</start><end>146</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit4"><titleInfo><title>Dose response of influenza A/Washington/ 897/80(H3N2) cold adapted reassortant virus in adult volunteers</title></titleInfo><name type="personal"><namePart type="given">ML</namePart><namePart type="family">Clements</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">RF</namePart><namePart type="family">Betts</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">HF</namePart><namePart type="family">Maassab</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BR</namePart><namePart type="family">Murphy</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Clements ML, Betts RF, Maassab HF, Murphy BR (1984b): Dose response of influenza A/Washington/ 897/80(H3N2) cold adapted reassortant virus in adult volunteers. Journal of Infectious Diseases 149: 814.</note><part><date>1984</date><detail type="volume"><caption>vol.</caption><number>149</number></detail><extent unit="pages"><start>814</start></extent></part><relatedItem type="host"><titleInfo><title>Journal of Infectious Diseases</title></titleInfo><part><date>1984</date><detail type="volume"><caption>vol.</caption><number>149</number></detail><extent unit="pages"><start>814</start></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="cit5"><titleInfo><title>Advantage of live attenuated cold adapted influenza A virus over inactivated vaccine for A/Washington/80(H3N2) wild type virus infection</title></titleInfo><name type="personal"><namePart type="given">ML</namePart><namePart type="family">Clements</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">RF</namePart><namePart type="family">Betts</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">BR</namePart><namePart type="family">Murphy</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Clements ML, Betts RF, Murphy BR (1984a): Advantage of live attenuated cold adapted influenza A virus over inactivated vaccine for A/Washington/80(H3N2) wild type virus infection. 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Journal of Infectious Diseases 146: 71–79.</note><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>146</number></detail><extent unit="pages"><start>71</start><end>79</end></extent></part><relatedItem type="host"><titleInfo><title>Journal of Infectious Diseases</title></titleInfo><part><date>1982</date><detail type="volume"><caption>vol.</caption><number>146</number></detail><extent unit="pages"><start>71</start><end>79</end></extent></part></relatedItem></relatedItem><identifier type="istex">DA95D4B0A16E872B4AE7E2BAC0D1D75D870D0613</identifier><identifier type="ark">ark:/67375/WNG-MSPH10MV-Q</identifier><identifier type="DOI">10.1002/jmv.1890260209</identifier><identifier type="ArticleID">JMV1890260209</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1988 Wiley‐Liss, Inc., A Wiley Company</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-L0C46X92-X">wiley</recordContentSource><recordOrigin>Converted from (version ) to MODS version 3.6.</recordOrigin><recordCreationDate encoding="w3cdtf">2019-11-15</recordCreationDate></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-MSPH10MV-Q/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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