Safety and Immunogenicity of a Recombinant Protein Influenza A Vaccine in Adult Human Volunteers and Protective Efficacy against Wild-Type H1N1 Virus Challenge
Identifieur interne : 001E68 ( Main/Exploration ); précédent : 001E67; suivant : 001E69Safety and Immunogenicity of a Recombinant Protein Influenza A Vaccine in Adult Human Volunteers and Protective Efficacy against Wild-Type H1N1 Virus Challenge
Auteurs : Louis F. Fries [États-Unis] ; Susan B. Dillon [États-Unis] ; James E. K. Hildreth [États-Unis] ; Ruth A. Karron [États-Unis] ; Ann W. Funkhouser [États-Unis] ; Carl J. Friedman [États-Unis] ; Christopher S. Jones [États-Unis] ; Vasantha G. Culleton [États-Unis] ; Mary Lou Clements [États-Unis]Source :
- Journal of Infectious Diseases [ 0022-1899 ] ; 1993.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Adolescent, Adulte, Adulte d'âge moyen, Analyse de variance, Anticorps antiviraux (biosynthèse), Excrétion virale, Facteurs temps, Glycoprotéine hémagglutinine du virus influenza, Grippe humaine (), Humains, Hémagglutinines virales (effets indésirables), Hémagglutinines virales (immunologie), Immunité cellulaire, Immunoglobuline G (biosynthèse), Lymphocytes T cytotoxiques, Protéines de l'enveloppe virale (immunologie), Protéines recombinantes, Protéines virales (effets indésirables), Protéines virales (immunologie), Relation dose-réponse (immunologie), Sous-type H1N1 du virus de la grippe A, Vaccins antigrippaux (effets indésirables), Vaccins antigrippaux (immunologie), Vaccins synthétiques (effets indésirables), Vaccins synthétiques (immunologie), Virus de la grippe A (immunologie), Études de cohortes.
- MESH :
- biosynthèse : Anticorps antiviraux, Immunoglobuline G.
- effets indésirables : Hémagglutinines virales, Protéines virales, Vaccins antigrippaux, Vaccins synthétiques.
- immunologie : Hémagglutinines virales, Protéines de l'enveloppe virale, Protéines virales, Vaccins antigrippaux, Vaccins synthétiques, Virus de la grippe A.
- Activation des lymphocytes, Adolescent, Adulte, Adulte d'âge moyen, Analyse de variance, Excrétion virale, Facteurs temps, Glycoprotéine hémagglutinine du virus influenza, Grippe humaine, Humains, Immunité cellulaire, Lymphocytes T cytotoxiques, Protéines recombinantes, Relation dose-réponse (immunologie), Sous-type H1N1 du virus de la grippe A, Études de cohortes.
- Pascal (Inist)
- Wicri :
- topic : Vaccin, Vaccination.
English descriptors
- KwdEn :
- Adolescent, Adult, Analysis of Variance, Antibodies, Viral (biosynthesis), Antibody, Cohort Studies, Dose-Response Relationship, Immunologic, Hemagglutinin Glycoproteins, Influenza Virus, Hemagglutinins, Viral (adverse effects), Hemagglutinins, Viral (immunology), Humans, Immunity, Cellular, Immunogenicity, Immunoglobulin G (biosynthesis), Immunological investigation, Influenza A, Influenza A Virus, H1N1 Subtype, Influenza A virus (immunology), Influenza Vaccines (adverse effects), Influenza Vaccines (immunology), Influenza, Human (prevention & control), Influenzavirus A, Lymphocyte Activation, Middle Aged, Recombinant Proteins, Serum, T-Lymphocytes, Cytotoxic, Time Factors, Toxicity, Vaccination, Vaccine, Vaccines, Synthetic (adverse effects), Vaccines, Synthetic (immunology), Viral Envelope Proteins (immunology), Viral Proteins (adverse effects), Viral Proteins (immunology), Virus Shedding.
- MESH :
- chemical , adverse effects : Hemagglutinins, Viral, Influenza Vaccines, Vaccines, Synthetic, Viral Proteins.
- chemical , biosynthesis : Antibodies, Viral, Immunoglobulin G.
- chemical , immunology : Hemagglutinins, Viral, Influenza Vaccines, Vaccines, Synthetic, Viral Envelope Proteins, Viral Proteins.
- immunology : Influenza A virus.
- prevention & control : Influenza, Human.
- Adolescent, Adult, Analysis of Variance, Cohort Studies, Dose-Response Relationship, Immunologic, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Immunity, Cellular, Influenza A Virus, H1N1 Subtype, Lymphocyte Activation, Middle Aged, Recombinant Proteins, T-Lymphocytes, Cytotoxic, Time Factors, Virus Shedding.
Abstract
A recombinant influenza A vaccine (D protein), comprising a carboxy-terminal sequence from the hemagglutinin HA2 subunit of A/Puerto Rico/8/34 virus (HINl, A/PR/34) fused to 81 amino-terminal residues of the NSI nonstructural protein, has previously protected mice against influenza A challenge by inducing HINl/H2N2 cross-reactive cytotoxic T cells (CTL) without hemagglutination-inhibiting (HI) or neutralizing antibody. In our dose-escalating study, the vaccine was safe in humans and induced both IgG and T cell proliferative responses to D protein but little antibody to A/PR/34 or A/Kawasakij8/86 (HINl, A/KW/86) viruses. Among an additional group of A/KW/86-seronegative volunteers immunized with 500 µg of D protein, none had a rise in serum HI or neutralizing antibody to A/KW/86, 20% had minimal IgG responses to A/KW/86 by EIA, and a minority had any increase in A/KW/86-specific CTL activity. However, viral shedding and clinical illness score were reduced in vaccinees relative to A/KW/86-seronegative unimmunized controls after intranasal challenge with wild-type A/KW/86. D protein immunization conferred significant protective immunity not currently explained by any of the immune parameters measured.
Url:
DOI: 10.1093/infdis/167.3.593
Affiliations:
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Fries</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Center for Immunization Research, Department ofInternational Health, School of Hygiene and Public Health, and Departments of Medicine and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Reprints or correspondence: Dr. Louis F. Fries, Center for Immunization Research, Room 125, Hampton House, 624 N, Broadway, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Dillon, Susan B" sort="Dillon, Susan B" uniqKey="Dillon S" first="Susan B." last="Dillon">Susan B. Dillon</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Center for Immunization Research, Department ofInternational Health, School of Hygiene and Public Health, and Departments of Medicine and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland</wicri:cityArea></affiliation></author><author><name sortKey="Hildreth, James E K" sort="Hildreth, James E K" uniqKey="Hildreth J" first="James E. K." last="Hildreth">James E. K. Hildreth</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Center for Immunization Research, Department ofInternational Health, School of Hygiene and Public Health, and Departments of Medicine and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland</wicri:cityArea></affiliation></author><author><name sortKey="Karron, Ruth A" sort="Karron, Ruth A" uniqKey="Karron R" first="Ruth A." last="Karron">Ruth A. 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Culleton</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Center for Immunization Research, Department ofInternational Health, School of Hygiene and Public Health, and Departments of Medicine and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland</wicri:cityArea></affiliation></author><author><name sortKey="Clements, Mary Lou" sort="Clements, Mary Lou" uniqKey="Clements M" first="Mary Lou" last="Clements">Mary Lou Clements</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Center for Immunization Research, Department ofInternational Health, School of Hygiene and Public Health, and Departments of Medicine and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Infectious Diseases</title><title level="j" type="abbrev">J Infect Dis.</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="1993-03">1993</date><biblScope unit="vol">167</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="593">593</biblScope><biblScope unit="page" to="601">601</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Analysis of Variance</term><term>Antibodies, Viral (biosynthesis)</term><term>Antibody</term><term>Cohort Studies</term><term>Dose-Response Relationship, Immunologic</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Hemagglutinins, Viral (adverse effects)</term><term>Hemagglutinins, Viral (immunology)</term><term>Humans</term><term>Immunity, Cellular</term><term>Immunogenicity</term><term>Immunoglobulin G (biosynthesis)</term><term>Immunological investigation</term><term>Influenza A</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A virus (immunology)</term><term>Influenza Vaccines (adverse effects)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (prevention & control)</term><term>Influenzavirus A</term><term>Lymphocyte Activation</term><term>Middle Aged</term><term>Recombinant Proteins</term><term>Serum</term><term>T-Lymphocytes, Cytotoxic</term><term>Time Factors</term><term>Toxicity</term><term>Vaccination</term><term>Vaccine</term><term>Vaccines, Synthetic (adverse effects)</term><term>Vaccines, Synthetic (immunology)</term><term>Viral Envelope Proteins (immunology)</term><term>Viral Proteins (adverse effects)</term><term>Viral Proteins (immunology)</term><term>Virus Shedding</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de variance</term><term>Anticorps antiviraux (biosynthèse)</term><term>Excrétion virale</term><term>Facteurs temps</term><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Grippe humaine ()</term><term>Humains</term><term>Hémagglutinines virales (effets indésirables)</term><term>Hémagglutinines virales (immunologie)</term><term>Immunité cellulaire</term><term>Immunoglobuline G (biosynthèse)</term><term>Lymphocytes T cytotoxiques</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Protéines recombinantes</term><term>Protéines virales (effets indésirables)</term><term>Protéines virales (immunologie)</term><term>Relation dose-réponse (immunologie)</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Vaccins antigrippaux (effets indésirables)</term><term>Vaccins antigrippaux (immunologie)</term><term>Vaccins synthétiques (effets indésirables)</term><term>Vaccins synthétiques (immunologie)</term><term>Virus de la grippe A (immunologie)</term><term>Études de cohortes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Hemagglutinins, Viral</term><term>Influenza Vaccines</term><term>Vaccines, Synthetic</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antibodies, Viral</term><term>Immunoglobulin G</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Hemagglutinins, Viral</term><term>Influenza Vaccines</term><term>Vaccines, Synthetic</term><term>Viral Envelope Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Anticorps antiviraux</term><term>Immunoglobuline G</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Hémagglutinines virales</term><term>Protéines virales</term><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Hémagglutinines virales</term><term>Protéines de l'enveloppe virale</term><term>Protéines virales</term><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A virus</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>Analysis of Variance</term><term>Cohort Studies</term><term>Dose-Response Relationship, Immunologic</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Humans</term><term>Immunity, Cellular</term><term>Influenza A Virus, H1N1 Subtype</term><term>Lymphocyte Activation</term><term>Middle Aged</term><term>Recombinant Proteins</term><term>T-Lymphocytes, Cytotoxic</term><term>Time Factors</term><term>Virus Shedding</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de variance</term><term>Excrétion virale</term><term>Facteurs temps</term><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Grippe humaine</term><term>Humains</term><term>Immunité cellulaire</term><term>Lymphocytes T cytotoxiques</term><term>Protéines recombinantes</term><term>Relation dose-réponse (immunologie)</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Études de cohortes</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Anticorps</term><term>Exploration immunologique</term><term>Grippe A</term><term>Immunogénicité</term><term>Influenzavirus A</term><term>Sérum</term><term>Toxicité</term><term>Vaccin</term><term>Vaccination</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">A recombinant influenza A vaccine (D protein), comprising a carboxy-terminal sequence from the hemagglutinin HA2 subunit of A/Puerto Rico/8/34 virus (HINl, A/PR/34) fused to 81 amino-terminal residues of the NSI nonstructural protein, has previously protected mice against influenza A challenge by inducing HINl/H2N2 cross-reactive cytotoxic T cells (CTL) without hemagglutination-inhibiting (HI) or neutralizing antibody. In our dose-escalating study, the vaccine was safe in humans and induced both IgG and T cell proliferative responses to D protein but little antibody to A/PR/34 or A/Kawasakij8/86 (HINl, A/KW/86) viruses. Among an additional group of A/KW/86-seronegative volunteers immunized with 500 µg of D protein, none had a rise in serum HI or neutralizing antibody to A/KW/86, 20% had minimal IgG responses to A/KW/86 by EIA, and a minority had any increase in A/KW/86-specific CTL activity. However, viral shedding and clinical illness score were reduced in vaccinees relative to A/KW/86-seronegative unimmunized controls after intranasal challenge with wild-type A/KW/86. D protein immunization conferred significant protective immunity not currently explained by any of the immune parameters measured.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Fries, Louis F" sort="Fries, Louis F" uniqKey="Fries L" first="Louis F." last="Fries">Louis F. Fries</name></region><name sortKey="Clements, Mary Lou" sort="Clements, Mary Lou" uniqKey="Clements M" first="Mary Lou" last="Clements">Mary Lou Clements</name><name sortKey="Culleton, Vasantha G" sort="Culleton, Vasantha G" uniqKey="Culleton V" first="Vasantha G." last="Culleton">Vasantha G. Culleton</name><name sortKey="Dillon, Susan B" sort="Dillon, Susan B" uniqKey="Dillon S" first="Susan B." last="Dillon">Susan B. Dillon</name><name sortKey="Friedman, Carl J" sort="Friedman, Carl J" uniqKey="Friedman C" first="Carl J." last="Friedman">Carl J. Friedman</name><name sortKey="Fries, Louis F" sort="Fries, Louis F" uniqKey="Fries L" first="Louis F." last="Fries">Louis F. Fries</name><name sortKey="Funkhouser, Ann W" sort="Funkhouser, Ann W" uniqKey="Funkhouser A" first="Ann W." last="Funkhouser">Ann W. Funkhouser</name><name sortKey="Hildreth, James E K" sort="Hildreth, James E K" uniqKey="Hildreth J" first="James E. K." last="Hildreth">James E. K. Hildreth</name><name sortKey="Jones, Christopher S" sort="Jones, Christopher S" uniqKey="Jones C" first="Christopher S." last="Jones">Christopher S. Jones</name><name sortKey="Karron, Ruth A" sort="Karron, Ruth A" uniqKey="Karron R" first="Ruth A." last="Karron">Ruth A. Karron</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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