{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:15:22Z","timestamp":1790716522141,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,1,15]],"date-time":"2016-01-15T00:00:00Z","timestamp":1452816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Influenza virus infection of nonhuman primates is a well-established animal model for studying pathogenesis and for evaluating prophylactic and therapeutic intervention strategies. However, usually a standard dose is used for the infection, and there is no information on the relation between challenge dose and virus replication or the induction of immune responses. Such information is also very scarce for humans and largely confined to evaluation of attenuated virus strains. Here, we have compared the effect of a commonly used dose (4 \u00d7 10\n            <jats:sup>6<\/jats:sup>\n            50% tissue culture infective doses) versus a 100-fold-higher dose, administered by intrabronchial installation, to two groups of 6 cynomolgus macaques. Animals infected with the high virus dose showed more fever and had higher peak levels of gamma interferon in the blood. However, virus replication in the trachea was not significantly different between the groups, although in 2 out of 6 animals from the high-dose group it was present at higher levels and for a longer duration. The virus-specific antibody response was not significantly different between the groups. However, antibody enzyme-linked immunosorbent assay, virus neutralization, and hemagglutination inhibition antibody titers correlated with cumulative virus production in the trachea. In conclusion, using influenza virus infection in cynomolgus macaques as a model, we demonstrated a relationship between the level of virus production upon infection and induction of functional antibody responses against the virus.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            There is only very limited information on the effect of virus inoculation dose on the level of virus production and the induction of adaptive immune responses in humans or nonhuman primates. We found only a marginal and variable effect of virus dose on virus production in the trachea but a significant effect on body temperature. The induction of functional antibody responses, including virus neutralization titer, hemagglutination inhibition titer, and antibody-dependent cell-mediated cytotoxicity, correlated with the level of virus replication measured in the trachea. The study reveals a relationship between virus production and functional antibody formation, which could be relevant in defining appropriate criteria for new influenza virus vaccine candidates.\n          <\/jats:p>","DOI":"10.1128\/jvi.02757-15","type":"journal-article","created":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T03:43:32Z","timestamp":1446695012000},"page":"1023-1033","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Correlation between Virus Replication and Antibody Responses in Macaques following Infection with Pandemic Influenza A Virus"],"prefix":"10.1128","volume":"90","author":[{"given":"Gerrit","family":"Koopman","sequence":"first","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Mooij","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"Dekking","sequence":"additional","affiliation":[{"name":"Crucell Holland B.V., Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblla","family":"Mortier","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne G.","family":"Nieuwenhuis","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"van Heteren","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmjan","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Crucell Holland B.V., Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond J.","family":"Remarque","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Rado\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Crucell Holland B.V., Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willy M. J. M.","family":"Bogers","sequence":"additional","affiliation":[{"name":"Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/v20801530"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.02.011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.148"},{"key":"e_1_3_2_5_2","first-page":"364","article-title":"A nonlethal young domesticated ferret (Mustela putorius furo) model for studying pandemic influenza virus A\/California\/04\/2009 (H1N1)","volume":"60","author":"Lednicky JA","year":"2010","unstructured":"Lednicky JA, Croutch CR, Lawrence SJ, Hamilton SB, Daniels DE, Astroff B. 2010. A nonlethal young domesticated ferret (Mustela putorius furo) model for studying pandemic influenza virus A\/California\/04\/2009 (H1N1). 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Thoracic radiography as a refinement methodology for the study of H1N1 influenza in cynomologus macaques (Macaca fascicularis). Comp Med 60:389\u2013395.","journal-title":"Comp Med"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01848-10"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126132"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00911-13"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020547"},{"key":"e_1_3_2_33_2","volume-title":"WHO manual on animal influenza diagnosis and surveillance","author":"World Health Organization","year":"2002","unstructured":"World Health Organization. 2002. WHO manual on animal influenza diagnosis and surveillance. 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MMRW Recommend Rep 55(RR10):1\u201342. http:\/\/www.cdc.gov\/MMWR\/preview\/mmwrhtml\/rr5510a1.htm."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3182367662"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000137566.87691.3b"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.15"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3350"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2612"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02757-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02757-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:12:45Z","timestamp":1646489565000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02757-15"}},"subtitle":[],"editor":[{"given":"S.","family":"Schultz-Cherry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,1,15]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,1,15]]}},"alternative-id":["10.1128\/JVI.02757-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02757-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,15]]},"assertion":[{"value":"2015-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}