Genetic stability of live attenuated vaccines against potentially pandemic influenza viruses.
Identifieur interne : 000063 ( PubMed/Corpus ); précédent : 000062; suivant : 000064Genetic stability of live attenuated vaccines against potentially pandemic influenza viruses.
Auteurs : Irina Kiseleva ; Irina Dubrovina ; Ekaterina Fedorova ; Natalie Larionova ; Irina Isakova-Sivak ; Ekaterina Bazhenova ; Maria Pisareva ; Victoria Kuznetsova ; Jorge Flores ; Larisa RudenkoSource :
- Vaccine [ 1873-2518 ] ; 2015.
English descriptors
- KwdEn :
- Adolescent, Adult, Animals, Chickens, DNA Mutational Analysis, Double-Blind Method, Female, Genome, Viral, Genomic Instability, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Humans, Influenza A Virus, H2N2 Subtype (genetics), Influenza A Virus, H2N2 Subtype (isolation & purification), Influenza A Virus, H5N2 Subtype (genetics), Influenza A Virus, H5N2 Subtype (isolation & purification), Influenza A Virus, H7N3 Subtype (genetics), Influenza A Virus, H7N3 Subtype (isolation & purification), Influenza Vaccines (administration & dosage), Influenza Vaccines (immunology), Influenza, Human (prevention & control), Male, Middle Aged, Ovum, Reassortant Viruses (genetics), Reassortant Viruses (isolation & purification), Vaccines, Attenuated (administration & dosage), Vaccines, Attenuated (immunology), Virus Replication, Virus Shedding, Young Adult.
- MESH :
- chemical , administration & dosage : Influenza Vaccines, Vaccines, Attenuated.
- chemical , genetics : Hemagglutinin Glycoproteins, Influenza Virus.
- genetics : Influenza A Virus, H2N2 Subtype, Influenza A Virus, H5N2 Subtype, Influenza A Virus, H7N3 Subtype, Reassortant Viruses.
- chemical , immunology : Influenza Vaccines, Vaccines, Attenuated.
- isolation & purification : Influenza A Virus, H2N2 Subtype, Influenza A Virus, H5N2 Subtype, Influenza A Virus, H7N3 Subtype, Reassortant Viruses.
- prevention & control : Influenza, Human.
- Adolescent, Adult, Animals, Chickens, DNA Mutational Analysis, Double-Blind Method, Female, Genome, Viral, Genomic Instability, Humans, Male, Middle Aged, Ovum, Virus Replication, Virus Shedding, Young Adult.
Abstract
Ensuring genetic stability is a prerequisite for live attenuated influenza vaccine (LAIV). This study describes the results of virus shedding and clinical isolates' testing of Phase I clinical trials of Russian LAIVs against potentially pandemic influenza viruses in healthy adults.
DOI: 10.1016/j.vaccine.2015.09.050
PubMed: 26432909
Links to Exploration step
pubmed:26432909Le document en format XML
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Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Fedorova, Ekaterina" sort="Fedorova, Ekaterina" uniqKey="Fedorova E" first="Ekaterina" last="Fedorova">Ekaterina Fedorova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Larionova, Natalie" sort="Larionova, Natalie" uniqKey="Larionova N" first="Natalie" last="Larionova">Natalie Larionova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Isakova Sivak, Irina" sort="Isakova Sivak, Irina" uniqKey="Isakova Sivak I" first="Irina" last="Isakova-Sivak">Irina Isakova-Sivak</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Bazhenova, Ekaterina" sort="Bazhenova, Ekaterina" uniqKey="Bazhenova E" first="Ekaterina" last="Bazhenova">Ekaterina Bazhenova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Pisareva, Maria" sort="Pisareva, Maria" uniqKey="Pisareva M" first="Maria" last="Pisareva">Maria Pisareva</name><affiliation><nlm:affiliation>Department of Molecular Virology, Institute of Influenza, St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Kuznetsova, Victoria" sort="Kuznetsova, Victoria" uniqKey="Kuznetsova V" first="Victoria" last="Kuznetsova">Victoria Kuznetsova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Flores, Jorge" sort="Flores, Jorge" uniqKey="Flores J" first="Jorge" last="Flores">Jorge Flores</name><affiliation><nlm:affiliation>PATH, Seattle, Washington, 98121, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26432909</idno><idno type="pmid">26432909</idno><idno type="doi">10.1016/j.vaccine.2015.09.050</idno><idno type="wicri:Area/PubMed/Corpus">000063</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000063</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Genetic stability of live attenuated vaccines against potentially pandemic influenza viruses.</title><author><name sortKey="Kiseleva, Irina" sort="Kiseleva, Irina" uniqKey="Kiseleva I" first="Irina" last="Kiseleva">Irina Kiseleva</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia. Electronic address: irina.v.kiseleva@mail.ru.</nlm:affiliation></affiliation></author><author><name sortKey="Dubrovina, Irina" sort="Dubrovina, Irina" uniqKey="Dubrovina I" first="Irina" last="Dubrovina">Irina Dubrovina</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Fedorova, Ekaterina" sort="Fedorova, Ekaterina" uniqKey="Fedorova E" first="Ekaterina" last="Fedorova">Ekaterina Fedorova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Larionova, Natalie" sort="Larionova, Natalie" uniqKey="Larionova N" first="Natalie" last="Larionova">Natalie Larionova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Isakova Sivak, Irina" sort="Isakova Sivak, Irina" uniqKey="Isakova Sivak I" first="Irina" last="Isakova-Sivak">Irina Isakova-Sivak</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Bazhenova, Ekaterina" sort="Bazhenova, Ekaterina" uniqKey="Bazhenova E" first="Ekaterina" last="Bazhenova">Ekaterina Bazhenova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Pisareva, Maria" sort="Pisareva, Maria" uniqKey="Pisareva M" first="Maria" last="Pisareva">Maria Pisareva</name><affiliation><nlm:affiliation>Department of Molecular Virology, Institute of Influenza, St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Kuznetsova, Victoria" sort="Kuznetsova, Victoria" uniqKey="Kuznetsova V" first="Victoria" last="Kuznetsova">Victoria Kuznetsova</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Flores, Jorge" sort="Flores, Jorge" uniqKey="Flores J" first="Jorge" last="Flores">Jorge Flores</name><affiliation><nlm:affiliation>PATH, Seattle, Washington, 98121, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name><affiliation><nlm:affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Vaccine</title><idno type="eISSN">1873-2518</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Animals</term><term>Chickens</term><term>DNA Mutational Analysis</term><term>Double-Blind Method</term><term>Female</term><term>Genome, Viral</term><term>Genomic Instability</term><term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term><term>Humans</term><term>Influenza A Virus, H2N2 Subtype (genetics)</term><term>Influenza A Virus, H2N2 Subtype (isolation & purification)</term><term>Influenza A Virus, H5N2 Subtype (genetics)</term><term>Influenza A Virus, H5N2 Subtype (isolation & purification)</term><term>Influenza A Virus, H7N3 Subtype (genetics)</term><term>Influenza A Virus, H7N3 Subtype (isolation & purification)</term><term>Influenza Vaccines (administration & dosage)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (prevention & control)</term><term>Male</term><term>Middle Aged</term><term>Ovum</term><term>Reassortant Viruses (genetics)</term><term>Reassortant Viruses (isolation & purification)</term><term>Vaccines, Attenuated (administration & dosage)</term><term>Vaccines, Attenuated (immunology)</term><term>Virus Replication</term><term>Virus Shedding</term><term>Young Adult</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term><term>Vaccines, Attenuated</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza A Virus, H5N2 Subtype</term><term>Influenza A Virus, H7N3 Subtype</term><term>Reassortant Viruses</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Influenza Vaccines</term><term>Vaccines, Attenuated</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza A Virus, H5N2 Subtype</term><term>Influenza A Virus, H7N3 Subtype</term><term>Reassortant Viruses</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Animals</term><term>Chickens</term><term>DNA Mutational Analysis</term><term>Double-Blind Method</term><term>Female</term><term>Genome, Viral</term><term>Genomic Instability</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Ovum</term><term>Virus Replication</term><term>Virus Shedding</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ensuring genetic stability is a prerequisite for live attenuated influenza vaccine (LAIV). This study describes the results of virus shedding and clinical isolates' testing of Phase I clinical trials of Russian LAIVs against potentially pandemic influenza viruses in healthy adults.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26432909</PMID><DateCompleted><Year>2016</Year><Month>08</Month><Day>20</Day></DateCompleted><DateRevised><Year>2015</Year><Month>12</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-2518</ISSN><JournalIssue CitedMedium="Internet"><Volume>33</Volume><Issue>49</Issue><PubDate><Year>2015</Year><Month>Dec</Month><Day>08</Day></PubDate></JournalIssue><Title>Vaccine</Title><ISOAbbreviation>Vaccine</ISOAbbreviation></Journal><ArticleTitle>Genetic stability of live attenuated vaccines against potentially pandemic influenza viruses.</ArticleTitle><Pagination><MedlinePgn>7008-14</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.vaccine.2015.09.050</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0264-410X(15)01326-2</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Ensuring genetic stability is a prerequisite for live attenuated influenza vaccine (LAIV). This study describes the results of virus shedding and clinical isolates' testing of Phase I clinical trials of Russian LAIVs against potentially pandemic influenza viruses in healthy adults.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Three live attenuated vaccines against potentially pandemic influenza viruses, H2N2 LAIV, H5N2 LAIV and H7N3 LAIV, generated by classical reassortment in eggs, were studied. For each vaccine tested, subjects were randomly distributed into two groups to receive two doses of either LAIV or placebo at a 3:1 vaccine/placebo ratio. Nasal swabs were examined for vaccine virus shedding by culturing in eggs and by PCR. Vaccine isolates were tested for temperature sensitivity and cold-adaptation (ts/ca phenotypes) and for nucleotide sequence.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The majority of nasal wash positive specimens were detected on the first day following vaccination. PCR method demonstrated higher sensitivity than routine virus isolation in eggs. None of the placebo recipients had detectable vaccine virus replication. All viruses isolated from the immunized subjects retained the ts/ca phenotypic characteristics of the master donor virus (MDV) and were shown to preserve all attenuating mutations described for the MDV. These data suggest high level of vaccine virus genetic stability after replication in humans. During manufacture process, no additional mutations occurred in the genome of H2N2 LAIV. In contrast, one amino acid change in the HA of H7N3 LAIV and two additional mutations in the HA of H5N2 LAIV manufactured vaccine lot were detected, however, they did not affect their ts/ca phenotypes.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our clinical trials revealed phenotypic and genetic stability of the LAIV viruses recovered from the immunized volunteers. In addition, no vaccine virus was detected in the placebo groups indicating the lack of person-to-person transmission. LAIV TRIAL REGISTRATION at ClinicalTrials.gov: H7N3-NCT01511419; H5N2-NCT01719783; H2N2-NCT01982331.</AbstractText><CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kiseleva</LastName><ForeName>Irina</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia. Electronic address: irina.v.kiseleva@mail.ru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dubrovina</LastName><ForeName>Irina</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fedorova</LastName><ForeName>Ekaterina</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Larionova</LastName><ForeName>Natalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Isakova-Sivak</LastName><ForeName>Irina</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bazhenova</LastName><ForeName>Ekaterina</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pisareva</LastName><ForeName>Maria</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular Virology, Institute of Influenza, St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuznetsova</LastName><ForeName>Victoria</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flores</LastName><ForeName>Jorge</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>PATH, Seattle, Washington, 98121, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rudenko</LastName><ForeName>Larisa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street , St Petersburg 197376, Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT01511419</AccessionNumber><AccessionNumber>NCT01719783</AccessionNumber><AccessionNumber>NCT01982331</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D017426">Clinical Trial, Phase I</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>10</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Vaccine</MedlineTA><NlmUniqueID>8406899</NlmUniqueID><ISSNLinking>0264-410X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019267">Hemagglutinin Glycoproteins, Influenza Virus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014613">Vaccines, Attenuated</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002645" MajorTopicYN="N">Chickens</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004252" MajorTopicYN="N">DNA Mutational Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016679" MajorTopicYN="Y">Genome, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042822" MajorTopicYN="Y">Genomic Instability</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019267" MajorTopicYN="N">Hemagglutinin Glycoproteins, Influenza Virus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" 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MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007251" MajorTopicYN="N">Influenza, Human</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010063" MajorTopicYN="N">Ovum</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016865" MajorTopicYN="N">Reassortant Viruses</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014613" MajorTopicYN="N">Vaccines, Attenuated</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017201" MajorTopicYN="Y">Virus Shedding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Genetic stability</Keyword><Keyword MajorTopicYN="N">Influenza</Keyword><Keyword MajorTopicYN="N">Live attenuated influenza vaccine</Keyword><Keyword MajorTopicYN="N">Pre-pandemic vaccine</Keyword><Keyword MajorTopicYN="N">Vaccine virus shedding</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>02</Month><Day>10</Day></PubMedPubDate><PubMedPubDate 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