Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers.
Identifieur interne : 002457 ( Main/Merge ); précédent : 002456; suivant : 002458Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers.
Auteurs : M H Snyder ; M L Clements ; R F Betts ; R. Dolin ; A J Buckler-White ; E L Tierney ; B R MurphySource :
- Journal of clinical microbiology [ 0095-1137 ] ; 1986.
Descripteurs français
- KwdFr :
- Adulte, Anticorps antiviraux (biosynthèse), Humains, Hémagglutinines virales (immunologie), Réplication virale, Sialidase (immunologie), Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Vaccins antiviraux (immunologie), Virus de la grippe A (croissance et développement), Virus de la grippe A (immunologie).
- MESH :
- biosynthèse : Anticorps antiviraux.
- croissance et développement : Virus de la grippe A.
- immunologie : Hémagglutinines virales, Sialidase, Vaccins antiviraux, Virus de la grippe A.
- Adulte, Humains, Réplication virale, Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A.
English descriptors
- KwdEn :
- Adult, Antibodies, Viral (biosynthesis), Hemagglutinins, Viral (immunology), Humans, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A virus (growth & development), Influenza A virus (immunology), Neuraminidase (immunology), Viral Vaccines (immunology), Virus Replication.
- MESH :
- chemical , biosynthesis : Antibodies, Viral.
- chemical , immunology : Hemagglutinins, Viral, Neuraminidase, Viral Vaccines.
- growth & development : Influenza A virus.
- immunology : Influenza A virus.
- Adult, Humans, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Virus Replication.
Abstract
An avian-human reassortant influenza A virus deriving its genes coding for the hemagglutinin and neuraminidase from the human influenza A/Washington/897/80 (H3N2) virus and its six "internal" genes from the avian influenza A/Mallard/NY/6750/78 (H2N2) virus (i.e., a six-gene reassortant) was previously shown to be safe, infectious, nontransmissible, and immunogenic as a live virus vaccine in adult humans. Two additional six-gene avian-human reassortant influenza viruses derived from the mating of wild-type human influenza A/California/10/78 (H1N1) and A/Korea/1/82 (H3N2) viruses with the avian influenza A/Mallard/NY/78 virus were evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:8) adult volunteers for safety, infectivity, and immunogenicity to determine whether human influenza A viruses can be reproducibly attenuated by the transfer of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The 50% human infectious dose was 10(4.9) 50% tissue culture infectious doses for the H1N1 reassortant virus and 10(5.4) 50% tissue culture infectious doses for the H3N2 reassortant virus. Both reassortants were satisfactorily attenuated with only 5% (H1N1) and 2% (H3N2) of infected vaccines receiving less than 400 50% human infectious doses developing illness. Consistent with this level of attenuation, the magnitude of viral shedding after inoculation was reduced 100-fold (H1N1) to 10,000-fold (H3N2) compared with that produced by wild-type virus. The duration of virus shedding by vaccines was one-third that of controls receiving wild-type virus. At 40 to 100 50% human infectious doses, virus-specific immune responses were seen in 77 to 93% of volunteers. When vaccinees who has received 10(7.5) 50% tissue culture infectious doses of the H3N2 vaccine were experimentally challenged with a homologous wild-type human virus only 2 of 19 (11%) vaccinees became ill compared with 7 of 14 (50%) unvaccinated seronegative controls ( P < 0.025; protective efficacy, 79%). Thus, three different virulent human influenza A viruses have been satisfactorily attenuated by the acquisition of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The observation that this donor virus can reproducibly attenuate human influenza A viruses indicates that avian-human influenza A reassortants should be further studied as potential live influenza A virus vaccines.
PubMed: 3711273
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pubmed:3711273Le document en format XML
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<author><name sortKey="Buckler White, A J" sort="Buckler White, A J" uniqKey="Buckler White A" first="A J" last="Buckler-White">A J Buckler-White</name>
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<author><name sortKey="Clements, M L" sort="Clements, M L" uniqKey="Clements M" first="M L" last="Clements">M L Clements</name>
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<term>Antibodies, Viral (biosynthesis)</term>
<term>Hemagglutinins, Viral (immunology)</term>
<term>Humans</term>
<term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza A Virus, H3N2 Subtype</term>
<term>Influenza A virus (growth & development)</term>
<term>Influenza A virus (immunology)</term>
<term>Neuraminidase (immunology)</term>
<term>Viral Vaccines (immunology)</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Anticorps antiviraux (biosynthèse)</term>
<term>Humains</term>
<term>Hémagglutinines virales (immunologie)</term>
<term>Réplication virale</term>
<term>Sialidase (immunologie)</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H3N2 du virus de la grippe A</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Virus de la grippe A (croissance et développement)</term>
<term>Virus de la grippe A (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antibodies, Viral</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Hemagglutinins, Viral</term>
<term>Neuraminidase</term>
<term>Viral Vaccines</term>
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<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Anticorps antiviraux</term>
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<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Virus de la grippe A</term>
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<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Influenza A virus</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Hémagglutinines virales</term>
<term>Sialidase</term>
<term>Vaccins antiviraux</term>
<term>Virus de la grippe A</term>
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<term>Humans</term>
<term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza A Virus, H3N2 Subtype</term>
<term>Virus Replication</term>
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<term>Humains</term>
<term>Réplication virale</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
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<front><div type="abstract" xml:lang="en">An avian-human reassortant influenza A virus deriving its genes coding for the hemagglutinin and neuraminidase from the human influenza A/Washington/897/80 (H3N2) virus and its six "internal" genes from the avian influenza A/Mallard/NY/6750/78 (H2N2) virus (i.e., a six-gene reassortant) was previously shown to be safe, infectious, nontransmissible, and immunogenic as a live virus vaccine in adult humans. Two additional six-gene avian-human reassortant influenza viruses derived from the mating of wild-type human influenza A/California/10/78 (H1N1) and A/Korea/1/82 (H3N2) viruses with the avian influenza A/Mallard/NY/78 virus were evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:8) adult volunteers for safety, infectivity, and immunogenicity to determine whether human influenza A viruses can be reproducibly attenuated by the transfer of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The 50% human infectious dose was 10(4.9) 50% tissue culture infectious doses for the H1N1 reassortant virus and 10(5.4) 50% tissue culture infectious doses for the H3N2 reassortant virus. Both reassortants were satisfactorily attenuated with only 5% (H1N1) and 2% (H3N2) of infected vaccines receiving less than 400 50% human infectious doses developing illness. Consistent with this level of attenuation, the magnitude of viral shedding after inoculation was reduced 100-fold (H1N1) to 10,000-fold (H3N2) compared with that produced by wild-type virus. The duration of virus shedding by vaccines was one-third that of controls receiving wild-type virus. At 40 to 100 50% human infectious doses, virus-specific immune responses were seen in 77 to 93% of volunteers. When vaccinees who has received 10(7.5) 50% tissue culture infectious doses of the H3N2 vaccine were experimentally challenged with a homologous wild-type human virus only 2 of 19 (11%) vaccinees became ill compared with 7 of 14 (50%) unvaccinated seronegative controls ( P < 0.025; protective efficacy, 79%). Thus, three different virulent human influenza A viruses have been satisfactorily attenuated by the acquisition of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The observation that this donor virus can reproducibly attenuate human influenza A viruses indicates that avian-human influenza A reassortants should be further studied as potential live influenza A virus vaccines.</div>
</front>
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