Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant.
Identifieur interne : 000440 ( PubMed/Corpus ); précédent : 000439; suivant : 000441Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant.
Auteurs : S B Dillon ; S G Demuth ; M A Schneider ; C B Weston ; C S Jones ; J F Young ; M. Scott ; P K Bhatnaghar ; S. Locastro ; N. HannaSource :
- Vaccine [ 0264-410X ] ; 1992.
English descriptors
- KwdEn :
- Adjuvants, Immunologic (pharmacology), Aluminum Hydroxide (pharmacology), Animals, CD4-Positive T-Lymphocytes (physiology), CD8 Antigens (analysis), Female, Histocompatibility Antigens Class I (immunology), Influenza Vaccines (immunology), Mice, Mice, Inbred Strains, T-Lymphocytes, Cytotoxic (physiology), Vaccines, Synthetic (immunology).
- MESH :
- chemical , analysis : CD8 Antigens.
- chemical , immunology : Histocompatibility Antigens Class I, Influenza Vaccines, Vaccines, Synthetic.
- chemical , pharmacology : Adjuvants, Immunologic, Aluminum Hydroxide.
- physiology : CD4-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic.
- Animals, Female, Mice, Mice, Inbred Strains.
Abstract
Induction of class I MHC-restricted cytotoxic T lymphocyte (CTL) responses by soluble proteins or peptides requires complex adjuvants or carrier systems which are not licensed for use with human vaccines. The data presented in this report show that vaccination with a highly purified recombinant influenza protein antigen in aluminium hydroxide adjuvant, the only adjuvant currently licensed for clinical use, elicited class I restricted CTL and protection from lethal challenge with H1N1 and H2N2 viruses. The antigen (D protein, SK&F 106160) is produced by expression of H1N1 influenza virus-derived cDNA (strain A/PR/8/34) in Escherichia coli, and is composed of the first 81 N-terminal amino acids (aa) of the non-structural protein 1 (NS1) fused via a nine nucleotide non-viral linker sequence to the 157 C-terminal aa of the haemagglutinin 2 subunit (HA2). Previous work by Kuwano et al demonstrated that in vitro stimulation of spleen cells from influenza virus-primed mice, with a partially purified preparation of the D protein, selected for CD8+ CTL clones which facilitated lung clearance of H1N1 and H2N2 viruses. In the current study, these results were extended by studying the responses of mice actively immunized with highly purified D protein in the presence or absence of adjuvants. Vaccination of CB6F1 (H-2dxb) mice with D protein in aluminum hydroxide or Freund's complete adjuvant generated H1N1 cross-reactive, H-2d-restricted, CD8+ CTL directed against an immunodominant HA2 epitope (aa 189-199). D protein without adjuvant did not elicit CTL, regardless of the route of injection. However, long-lived (greater than 6 months) splenic memory CTL were elicited by boosting mice intraperitoneally (i.p.) with the D protein in the absence of adjuvant. In mice injected subcutaneously with D protein in aluminium hydroxide at weeks 0 and 3, survival was increased relative to controls up to 16 weeks beyond the second vaccination, after which time additional boosting was required for protection. Studies in H-2b and H-2k mice vaccinated with the D protein showed that induction of CD4+ T-cell or antibody responses, in the absence of CD8+ CTL, did not correlate with protection. Passive transfer of immune sera from CB6F1 mice was also not protective. This prototype H1N1 recombinant subunit vaccine in aluminium adjuvant should directly address the feasibility of achieving a protective cell-mediated immune response in human influenza.
DOI: 10.1016/0264-410x(92)90369-u
PubMed: 1349448
Links to Exploration step
pubmed:1349448Le document en format XML
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Scott</name></author><author><name sortKey="Bhatnaghar, P K" sort="Bhatnaghar, P K" uniqKey="Bhatnaghar P" first="P K" last="Bhatnaghar">P K Bhatnaghar</name></author><author><name sortKey="Locastro, S" sort="Locastro, S" uniqKey="Locastro S" first="S" last="Locastro">S. Locastro</name></author><author><name sortKey="Hanna, N" sort="Hanna, N" uniqKey="Hanna N" first="N" last="Hanna">N. Hanna</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1992">1992</date><idno type="RBID">pubmed:1349448</idno><idno type="pmid">1349448</idno><idno type="doi">10.1016/0264-410x(92)90369-u</idno><idno type="wicri:Area/PubMed/Corpus">000440</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000440</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant.</title><author><name sortKey="Dillon, S B" sort="Dillon, S B" uniqKey="Dillon S" first="S B" last="Dillon">S B Dillon</name><affiliation><nlm:affiliation>Department of Anti-Infectives, Smith-Kline Beecham Pharmaceuticals, King of Prussia, PA 19406.</nlm:affiliation></affiliation></author><author><name sortKey="Demuth, S G" sort="Demuth, S G" uniqKey="Demuth S" first="S G" last="Demuth">S G Demuth</name></author><author><name sortKey="Schneider, M A" sort="Schneider, M A" uniqKey="Schneider M" first="M A" last="Schneider">M A Schneider</name></author><author><name sortKey="Weston, C B" sort="Weston, C B" uniqKey="Weston C" first="C B" last="Weston">C B Weston</name></author><author><name sortKey="Jones, C S" sort="Jones, C S" uniqKey="Jones C" first="C S" last="Jones">C S Jones</name></author><author><name sortKey="Young, J F" sort="Young, J F" uniqKey="Young J" first="J F" last="Young">J F Young</name></author><author><name sortKey="Scott, M" sort="Scott, M" uniqKey="Scott M" first="M" last="Scott">M. Scott</name></author><author><name sortKey="Bhatnaghar, P K" sort="Bhatnaghar, P K" uniqKey="Bhatnaghar P" first="P K" last="Bhatnaghar">P K Bhatnaghar</name></author><author><name sortKey="Locastro, S" sort="Locastro, S" uniqKey="Locastro S" first="S" last="Locastro">S. Locastro</name></author><author><name sortKey="Hanna, N" sort="Hanna, N" uniqKey="Hanna N" first="N" last="Hanna">N. Hanna</name></author></analytic><series><title level="j">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="1992" type="published">1992</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adjuvants, Immunologic (pharmacology)</term><term>Aluminum Hydroxide (pharmacology)</term><term>Animals</term><term>CD4-Positive T-Lymphocytes (physiology)</term><term>CD8 Antigens (analysis)</term><term>Female</term><term>Histocompatibility Antigens Class I (immunology)</term><term>Influenza Vaccines (immunology)</term><term>Mice</term><term>Mice, Inbred Strains</term><term>T-Lymphocytes, Cytotoxic (physiology)</term><term>Vaccines, Synthetic (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>CD8 Antigens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Histocompatibility Antigens Class I</term><term>Influenza Vaccines</term><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adjuvants, Immunologic</term><term>Aluminum Hydroxide</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>T-Lymphocytes, Cytotoxic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Mice</term><term>Mice, Inbred Strains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Induction of class I MHC-restricted cytotoxic T lymphocyte (CTL) responses by soluble proteins or peptides requires complex adjuvants or carrier systems which are not licensed for use with human vaccines. The data presented in this report show that vaccination with a highly purified recombinant influenza protein antigen in aluminium hydroxide adjuvant, the only adjuvant currently licensed for clinical use, elicited class I restricted CTL and protection from lethal challenge with H1N1 and H2N2 viruses. The antigen (D protein, SK&F 106160) is produced by expression of H1N1 influenza virus-derived cDNA (strain A/PR/8/34) in Escherichia coli, and is composed of the first 81 N-terminal amino acids (aa) of the non-structural protein 1 (NS1) fused via a nine nucleotide non-viral linker sequence to the 157 C-terminal aa of the haemagglutinin 2 subunit (HA2). Previous work by Kuwano et al demonstrated that in vitro stimulation of spleen cells from influenza virus-primed mice, with a partially purified preparation of the D protein, selected for CD8+ CTL clones which facilitated lung clearance of H1N1 and H2N2 viruses. In the current study, these results were extended by studying the responses of mice actively immunized with highly purified D protein in the presence or absence of adjuvants. Vaccination of CB6F1 (H-2dxb) mice with D protein in aluminum hydroxide or Freund's complete adjuvant generated H1N1 cross-reactive, H-2d-restricted, CD8+ CTL directed against an immunodominant HA2 epitope (aa 189-199). D protein without adjuvant did not elicit CTL, regardless of the route of injection. However, long-lived (greater than 6 months) splenic memory CTL were elicited by boosting mice intraperitoneally (i.p.) with the D protein in the absence of adjuvant. In mice injected subcutaneously with D protein in aluminium hydroxide at weeks 0 and 3, survival was increased relative to controls up to 16 weeks beyond the second vaccination, after which time additional boosting was required for protection. Studies in H-2b and H-2k mice vaccinated with the D protein showed that induction of CD4+ T-cell or antibody responses, in the absence of CD8+ CTL, did not correlate with protection. Passive transfer of immune sera from CB6F1 mice was also not protective. This prototype H1N1 recombinant subunit vaccine in aluminium adjuvant should directly address the feasibility of achieving a protective cell-mediated immune response in human influenza.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">1349448</PMID><DateCompleted><Year>1992</Year><Month>06</Month><Day>02</Day></DateCompleted><DateRevised><Year>2019</Year><Month>07</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0264-410X</ISSN><JournalIssue CitedMedium="Print"><Volume>10</Volume><Issue>5</Issue><PubDate><Year>1992</Year></PubDate></JournalIssue><Title>Vaccine</Title><ISOAbbreviation>Vaccine</ISOAbbreviation></Journal><ArticleTitle>Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant.</ArticleTitle><Pagination><MedlinePgn>309-18</MedlinePgn></Pagination><Abstract><AbstractText>Induction of class I MHC-restricted cytotoxic T lymphocyte (CTL) responses by soluble proteins or peptides requires complex adjuvants or carrier systems which are not licensed for use with human vaccines. The data presented in this report show that vaccination with a highly purified recombinant influenza protein antigen in aluminium hydroxide adjuvant, the only adjuvant currently licensed for clinical use, elicited class I restricted CTL and protection from lethal challenge with H1N1 and H2N2 viruses. The antigen (D protein, SK&F 106160) is produced by expression of H1N1 influenza virus-derived cDNA (strain A/PR/8/34) in Escherichia coli, and is composed of the first 81 N-terminal amino acids (aa) of the non-structural protein 1 (NS1) fused via a nine nucleotide non-viral linker sequence to the 157 C-terminal aa of the haemagglutinin 2 subunit (HA2). Previous work by Kuwano et al demonstrated that in vitro stimulation of spleen cells from influenza virus-primed mice, with a partially purified preparation of the D protein, selected for CD8+ CTL clones which facilitated lung clearance of H1N1 and H2N2 viruses. In the current study, these results were extended by studying the responses of mice actively immunized with highly purified D protein in the presence or absence of adjuvants. Vaccination of CB6F1 (H-2dxb) mice with D protein in aluminum hydroxide or Freund's complete adjuvant generated H1N1 cross-reactive, H-2d-restricted, CD8+ CTL directed against an immunodominant HA2 epitope (aa 189-199). D protein without adjuvant did not elicit CTL, regardless of the route of injection. However, long-lived (greater than 6 months) splenic memory CTL were elicited by boosting mice intraperitoneally (i.p.) with the D protein in the absence of adjuvant. In mice injected subcutaneously with D protein in aluminium hydroxide at weeks 0 and 3, survival was increased relative to controls up to 16 weeks beyond the second vaccination, after which time additional boosting was required for protection. Studies in H-2b and H-2k mice vaccinated with the D protein showed that induction of CD4+ T-cell or antibody responses, in the absence of CD8+ CTL, did not correlate with protection. Passive transfer of immune sera from CB6F1 mice was also not protective. This prototype H1N1 recombinant subunit vaccine in aluminium adjuvant should directly address the feasibility of achieving a protective cell-mediated immune response in human influenza.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dillon</LastName><ForeName>S B</ForeName><Initials>SB</Initials><AffiliationInfo><Affiliation>Department of Anti-Infectives, Smith-Kline Beecham Pharmaceuticals, King of Prussia, PA 19406.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Demuth</LastName><ForeName>S G</ForeName><Initials>SG</Initials></Author><Author ValidYN="Y"><LastName>Schneider</LastName><ForeName>M A</ForeName><Initials>MA</Initials></Author><Author ValidYN="Y"><LastName>Weston</LastName><ForeName>C B</ForeName><Initials>CB</Initials></Author><Author ValidYN="Y"><LastName>Jones</LastName><ForeName>C S</ForeName><Initials>CS</Initials></Author><Author ValidYN="Y"><LastName>Young</LastName><ForeName>J F</ForeName><Initials>JF</Initials></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Bhatnaghar</LastName><ForeName>P K</ForeName><Initials>PK</Initials></Author><Author ValidYN="Y"><LastName>LoCastro</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Hanna</LastName><ForeName>N</ForeName><Initials>N</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Vaccine</MedlineTA><NlmUniqueID>8406899</NlmUniqueID><ISSNLinking>0264-410X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000276">Adjuvants, Immunologic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016827">CD8 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MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016827" MajorTopicYN="N">CD8 Antigens</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015395" MajorTopicYN="N">Histocompatibility Antigens Class I</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008815" MajorTopicYN="N">Mice, Inbred Strains</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013602" MajorTopicYN="N">T-Lymphocytes, Cytotoxic</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014614" MajorTopicYN="N">Vaccines, Synthetic</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1992</Year><Month>1</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1992</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1992</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">1349448</ArticleId><ArticleId IdType="pii">0264-410X(92)90369-U</ArticleId><ArticleId IdType="doi">10.1016/0264-410x(92)90369-u</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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