Serveur d'exploration H2N2

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Development and Pre-Clinical Evaluation of Two LAIV Strains against Potentially Pandemic H2N2 Influenza Virus

Identifieur interne : 000043 ( 1968/Analysis ); précédent : 000042; suivant : 000044

Development and Pre-Clinical Evaluation of Two LAIV Strains against Potentially Pandemic H2N2 Influenza Virus

Auteurs : Irina Isakova-Sivak [Russie] ; J Rgen De Jonge [Pays-Bas] ; Tatiana Smolonogina [Russie] ; Andrey Rekstin [Russie] ; Geert Van Amerongen [Pays-Bas] ; Harry Van Dijken [Pays-Bas] ; Justin Mouthaan [Pays-Bas] ; Paul Roholl [Pays-Bas] ; Victoria Kuznetsova [Russie] ; Elena Doroshenko [Russie] ; Vadim Tsvetnitsky [États-Unis] ; Larisa Rudenko [Russie]

Source :

RBID : PMC:4109939

Descripteurs français

English descriptors

Abstract

H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.


Url:
DOI: 10.1371/journal.pone.0102339
PubMed: 25058039
PubMed Central: 4109939


Affiliations:


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PMC:4109939

Le document en format XML

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<name sortKey="Kuznetsova, Victoria" sort="Kuznetsova, Victoria" uniqKey="Kuznetsova V" first="Victoria" last="Kuznetsova">Victoria Kuznetsova</name>
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<addr-line>PATH Vaccine Development Global Program, Seattle, Washington, United States of America</addr-line>
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<name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name>
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<name sortKey="Isakova Sivak, Irina" sort="Isakova Sivak, Irina" uniqKey="Isakova Sivak I" first="Irina" last="Isakova-Sivak">Irina Isakova-Sivak</name>
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<name sortKey="Smolonogina, Tatiana" sort="Smolonogina, Tatiana" uniqKey="Smolonogina T" first="Tatiana" last="Smolonogina">Tatiana Smolonogina</name>
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<addr-line>Institute for Experimental Medicine, Saint Petersburg, Russia</addr-line>
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<name sortKey="Rekstin, Andrey" sort="Rekstin, Andrey" uniqKey="Rekstin A" first="Andrey" last="Rekstin">Andrey Rekstin</name>
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<name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name>
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<name sortKey="Van Dijken, Harry" sort="Van Dijken, Harry" uniqKey="Van Dijken H" first="Harry" last="Van Dijken">Harry Van Dijken</name>
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<addr-line>Centre for Infectious Disease Control, RIVM, Bilthoven, the Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<name sortKey="Mouthaan, Justin" sort="Mouthaan, Justin" uniqKey="Mouthaan J" first="Justin" last="Mouthaan">Justin Mouthaan</name>
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<nlm:aff id="aff2">
<addr-line>Centre for Infectious Disease Control, RIVM, Bilthoven, the Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Centre for Infectious Disease Control, RIVM, Bilthoven</wicri:regionArea>
<wicri:noRegion>Bilthoven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Roholl, Paul" sort="Roholl, Paul" uniqKey="Roholl P" first="Paul" last="Roholl">Paul Roholl</name>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<addr-line>Microscope Consultancy, Weesp, the Netherlands</addr-line>
</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Microscope Consultancy, Weesp</wicri:regionArea>
<wicri:noRegion>Weesp</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kuznetsova, Victoria" sort="Kuznetsova, Victoria" uniqKey="Kuznetsova V" first="Victoria" last="Kuznetsova">Victoria Kuznetsova</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Institute for Experimental Medicine, Saint Petersburg, Russia</addr-line>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Institute for Experimental Medicine, Saint Petersburg</wicri:regionArea>
<wicri:noRegion>Saint Petersburg</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Doroshenko, Elena" sort="Doroshenko, Elena" uniqKey="Doroshenko E" first="Elena" last="Doroshenko">Elena Doroshenko</name>
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<nlm:aff id="aff1">
<addr-line>Institute for Experimental Medicine, Saint Petersburg, Russia</addr-line>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Institute for Experimental Medicine, Saint Petersburg</wicri:regionArea>
<wicri:noRegion>Saint Petersburg</wicri:noRegion>
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<name sortKey="Tsvetnitsky, Vadim" sort="Tsvetnitsky, Vadim" uniqKey="Tsvetnitsky V" first="Vadim" last="Tsvetnitsky">Vadim Tsvetnitsky</name>
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<addr-line>PATH Vaccine Development Global Program, Seattle, Washington, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>PATH Vaccine Development Global Program, Seattle, Washington</wicri:regionArea>
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<region type="state">Washington (État)</region>
</placeName>
</affiliation>
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<name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name>
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<nlm:aff id="aff1">
<addr-line>Institute for Experimental Medicine, Saint Petersburg, Russia</addr-line>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Institute for Experimental Medicine, Saint Petersburg</wicri:regionArea>
<wicri:noRegion>Saint Petersburg</wicri:noRegion>
</affiliation>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Antibodies, Neutralizing (blood)</term>
<term>Antibodies, Viral (blood)</term>
<term>Drug Evaluation, Preclinical</term>
<term>Female</term>
<term>Ferrets</term>
<term>Gene Expression</term>
<term>Hemagglutinins, Viral (genetics)</term>
<term>Hemagglutinins, Viral (immunology)</term>
<term>Humans</term>
<term>Immunization</term>
<term>Influenza A Virus, H2N2 Subtype (immunology)</term>
<term>Influenza Vaccines (administration & dosage)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Lung (drug effects)</term>
<term>Lung (immunology)</term>
<term>Lung (virology)</term>
<term>Mice</term>
<term>Mice, Inbred CBA</term>
<term>Neuraminidase (genetics)</term>
<term>Neuraminidase (immunology)</term>
<term>Nose (drug effects)</term>
<term>Nose (immunology)</term>
<term>Nose (virology)</term>
<term>Orthomyxoviridae Infections (immunology)</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
<term>Orthomyxoviridae Infections (virology)</term>
<term>Pandemics (prevention & control)</term>
<term>Reassortant Viruses (genetics)</term>
<term>Reassortant Viruses (immunology)</term>
<term>Vaccines, Attenuated</term>
<term>Virus Replication</term>
</keywords>
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<term>Animaux</term>
<term>Anticorps antiviraux (sang)</term>
<term>Anticorps neutralisants (sang)</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Furets</term>
<term>Humains</term>
<term>Hémagglutinines virales (génétique)</term>
<term>Hémagglutinines virales (immunologie)</term>
<term>Immunisation</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Infections à Orthomyxoviridae (immunologie)</term>
<term>Infections à Orthomyxoviridae (virologie)</term>
<term>Nez ()</term>
<term>Nez (immunologie)</term>
<term>Nez (virologie)</term>
<term>Pandémies ()</term>
<term>Poumon ()</term>
<term>Poumon (immunologie)</term>
<term>Poumon (virologie)</term>
<term>Réplication virale</term>
<term>Sialidase (génétique)</term>
<term>Sialidase (immunologie)</term>
<term>Souris</term>
<term>Souris de lignée CBA</term>
<term>Sous-type H2N2 du virus de la grippe A (immunologie)</term>
<term>Vaccins antigrippaux (administration et posologie)</term>
<term>Vaccins antigrippaux (génétique)</term>
<term>Vaccins antigrippaux (immunologie)</term>
<term>Vaccins atténués</term>
<term>Virus recombinants (génétique)</term>
<term>Virus recombinants (immunologie)</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Influenza Vaccines</term>
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<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Hemagglutinins, Viral</term>
<term>Influenza Vaccines</term>
<term>Neuraminidase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Hemagglutinins, Viral</term>
<term>Influenza Vaccines</term>
<term>Neuraminidase</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Vaccins antigrippaux</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Lung</term>
<term>Nose</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Reassortant Viruses</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Hémagglutinines virales</term>
<term>Sialidase</term>
<term>Vaccins antigrippaux</term>
<term>Virus recombinants</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Hémagglutinines virales</term>
<term>Infections à Orthomyxoviridae</term>
<term>Nez</term>
<term>Poumon</term>
<term>Sialidase</term>
<term>Sous-type H2N2 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Virus recombinants</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Influenza A Virus, H2N2 Subtype</term>
<term>Lung</term>
<term>Nose</term>
<term>Orthomyxoviridae Infections</term>
<term>Reassortant Viruses</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Orthomyxoviridae Infections</term>
<term>Pandemics</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Infections à Orthomyxoviridae</term>
<term>Nez</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Lung</term>
<term>Nose</term>
<term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Drug Evaluation, Preclinical</term>
<term>Female</term>
<term>Ferrets</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Immunization</term>
<term>Mice</term>
<term>Mice, Inbred CBA</term>
<term>Vaccines, Attenuated</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Expression des gènes</term>
<term>Femelle</term>
<term>Furets</term>
<term>Humains</term>
<term>Immunisation</term>
<term>Infections à Orthomyxoviridae</term>
<term>Nez</term>
<term>Pandémies</term>
<term>Poumon</term>
<term>Réplication virale</term>
<term>Souris</term>
<term>Souris de lignée CBA</term>
<term>Vaccins atténués</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.</p>
</div>
</front>
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<name sortKey="Yang, Cf" uniqKey="Yang C">CF Yang</name>
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<author>
<name sortKey="Jin, H" uniqKey="Jin H">H Jin</name>
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<author>
<name sortKey="Kemble, G" uniqKey="Kemble G">G Kemble</name>
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<name sortKey="Chen, Gl" uniqKey="Chen G">GL Chen</name>
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<author>
<name sortKey="Lamirande, Ew" uniqKey="Lamirande E">EW Lamirande</name>
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<author>
<name sortKey="Jin, H" uniqKey="Jin H">H Jin</name>
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<author>
<name sortKey="Kemble, G" uniqKey="Kemble G">G Kemble</name>
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<author>
<name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
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<author>
<name sortKey="Liang, Ph" uniqKey="Liang P">PH Liang</name>
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<author>
<name sortKey="Luke, Cj" uniqKey="Luke C">CJ Luke</name>
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<name sortKey="Luke, Cj" uniqKey="Luke C">CJ Luke</name>
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<name sortKey="Cheng, X" uniqKey="Cheng X">X Cheng</name>
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<author>
<name sortKey="Jin, H" uniqKey="Jin H">H Jin</name>
</author>
<author>
<name sortKey="Subbarao, K" uniqKey="Subbarao K">K Subbarao</name>
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<name sortKey="Rockman, S" uniqKey="Rockman S">S Rockman</name>
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<author>
<name sortKey="Barr, Ig" uniqKey="Barr I">IG Barr</name>
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<author>
<name sortKey="Gilbertson, B" uniqKey="Gilbertson B">B Gilbertson</name>
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<author>
<name sortKey="Lowther, S" uniqKey="Lowther S">S Lowther</name>
</author>
</analytic>
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<name sortKey="Katz, Jm" uniqKey="Katz J">JM Katz</name>
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<author>
<name sortKey="Tumpey, Tm" uniqKey="Tumpey T">TM Tumpey</name>
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<name sortKey="Bodewes, R" uniqKey="Bodewes R">R Bodewes</name>
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<name sortKey="Rimmelzwaan, Gf" uniqKey="Rimmelzwaan G">GF Rimmelzwaan</name>
</author>
<author>
<name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name>
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<country>
<li>Pays-Bas</li>
<li>Russie</li>
<li>États-Unis</li>
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<li>Washington (État)</li>
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<name sortKey="Isakova Sivak, Irina" sort="Isakova Sivak, Irina" uniqKey="Isakova Sivak I" first="Irina" last="Isakova-Sivak">Irina Isakova-Sivak</name>
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<name sortKey="Doroshenko, Elena" sort="Doroshenko, Elena" uniqKey="Doroshenko E" first="Elena" last="Doroshenko">Elena Doroshenko</name>
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<name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name>
<name sortKey="Smolonogina, Tatiana" sort="Smolonogina, Tatiana" uniqKey="Smolonogina T" first="Tatiana" last="Smolonogina">Tatiana Smolonogina</name>
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<name sortKey="Roholl, Paul" sort="Roholl, Paul" uniqKey="Roholl P" first="Paul" last="Roholl">Paul Roholl</name>
<name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name>
<name sortKey="Van Dijken, Harry" sort="Van Dijken, Harry" uniqKey="Van Dijken H" first="Harry" last="Van Dijken">Harry Van Dijken</name>
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<name sortKey="Tsvetnitsky, Vadim" sort="Tsvetnitsky, Vadim" uniqKey="Tsvetnitsky V" first="Vadim" last="Tsvetnitsky">Vadim Tsvetnitsky</name>
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</affiliations>
</record>

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