Anti-viral chemotherapy plays an important part in treating and preventing influenza illness. However, its effectiveness in severe infections can be debated and a reoccurring problem is the emergence of resistant virus. Passive immunisation has for a long time been and is still used for prophylaxis and treatment of a number of infectious diseases. In this experimental study anti-influenza antibodies were passively administrated to mice, subsequently they were infected with influenza virus and treated with oseltamivir. The aim was to investigate, if anti-influenza antibodies influenced the out come of oseltamivir treatment and development of resistance towards oseltamivir. We show, that oseltamivir alone was not able to effectively prevent a fatal outcome, but that oseltamivir administered together with a limited amount of antibodies, resulted in improvement of the clinical condition of the mice. The results also showed that a higher dosage of antibodies alone were able to protect the mice from a lethal dose of virus. These findings suggest that the effectiveness of oseltamivir depends on the host’s immune response to the influenza virus, and that that passive immunization is an option that should be considered in the in control of influenza.
KeywordsExperimental InfluenzaPassively Administrated AntibodiesConvalescent PlasmaPassive ImmunisationOseltamivirLethal InfectionPolyclonal IgGPandemic Control
Luke, T., et al. (2010) Hark back: passive immunotherapy for influenza and other serious infections. Critical Care Medicine, 38, e66-73. doi:10.1097/CCM.0b013e3181d44c1e
Hoi, K.W., et al. (2010) Practical limitations of convalescent plasma collection: A case scenario in pandemic preparation for influenza A (H1N1) infection. Transfusion, 50, 1967-1971. doi:10.1111/j.1537-2995.2010.02651.x
Kreil, T.R., et al. (2012) Preparation of commercial quantities of a hyperimmune human intravenous immunoglobulin preparation against an emerging infectious disease: The example of pandemic H1N1 influenza. Transfusion, 52, 803-809. doi:10.1111/j.1537-2995.2011.03347.x
Parry, R.P., et al. (2012) Strategies for screening blood donors to source convalescent H1N1v plasma for intervention therapy. Vox Sanguinis, 103, 107-112. doi:10.1111/j.1423-0410.2012.01599.x
Wu, J.T., et al. (2010) Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic. Proceedings of the National Academy of Sciences, 107, 3269-3274. doi:10.1073/pnas.0911596107
Leider, J.P., et al. (2010) Convalescent transfusion for pandemic influenza: Preparing blood banks for a new plasma product? Transfusion, 50, 1384-1398. doi:10.1111/j.1537-2995.2010.02590.x
Kong, L. and Zhou, B. (2006) Successful treatment of avian influenza with convalescent plasma. Hong Kong Medical Journal, 12, 489.
Zhou, B., et al. (2007) Treatment with convalescent plasma for influenza A (H5N1) infection. New England Journal of Medicine, 357, 1450-1451. doi:10.1056/NEJMc070359
Hung, I.F., et al. (2011) Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clinical Infectious Diseases, 52, 447-456. doi:10.1093/cid/ciq106
Gordon, C.L., et al. (2010) Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G2 subclass deficiency. Clinical Infectious Diseases, 50, 672-678. doi:10.1086/650462
Wang, H., et al. (2008) Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. The Lancet, 371, 1427-1434. doi:10.1016/S0140-6736(08)60493-6
Yu, H., et al. (2008) Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in china. PLoS ONE, 3, e2985. doi:10.1371/journal.pone.0002985
Boon, A.C.M., et al. (2010) Cross-reactive neutralizing antibodies directed against pandemic H1N1 2009 virus are protective in a highly sensitive DBA/2 mouse influenza model. Journal of Virology, 84, 7662-7667. doi:10.1128/JVI.02444-09
Corti, D., et al. (2011) A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science, 333, 850-856. doi:10.1126/science.1205669
Hessel, A., et al. (2010) A pandemic influenza H1N1 live vaccine based on modified vaccinia ankara is highly immunogenic and protects mice in active and passive immunizations. PLoS ONE, 5, e12217. doi:10.1371/journal.pone.0012217
Howard, M.K., et al. (2011) H5N1 whole-virus vaccine induces neutralizing antibodies in humans which are protective in a mouse passive transfer model. PLoS ONE, 6, e23791. doi:10.1371/journal.pone.0012217
Kistner, O., et al. (2010) A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models. PLoS ONE, 5, e9349. doi:10.1371/journal.pone.0009349
Nguyen, H.H., et al. (2010) prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice. PLoS ONE, 5, e10152. doi:10.1371/journal.pone.0010152
Shahzad, M., et al. (2008) Passive immunization against highly patho-genic Avian Influenza Virus (AIV) strain H7N3 with antiserum generated from viral polypeptides protect poultry birds from lethal viral infection. Virology Journal, 5, 144. doi:10.1186/1743-422X-5-144
Ekiert, D.C., et al. (2009) Antibody recognition of a highly conserved influenza virus epitope. Science, 324, 246-251. doi:10.1126/science.1171491
Friesen, R.H.E., et al. (2010) New class of monoclonal antibodies against severe influenza: Prophylactic and therapeutic efficacy in ferrets. PLoS ONE, 5, e9106. doi:10.1371/journal.pone.0009106
Oh, H.L.J., et al. (2010) An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 Influenza Viruses. Journal of Virology, 84, 8275-8286. doi:10.1128/JVI.02593-09
Ward, P., et al. (2005) Oseltamivir (Tamiflu?) and its potential for use in the event of an influenza pandemic. Journal of Antimicrobial Chemotherapy, 55, 5-21. doi:10.1093/jac/dki018
Gubareva, L.V., et al. (2001) Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. Journal of Infectious Diseases, 183, 523-531. doi:10.1086/318537
Kiso, M., et al. (2004) Resistant influenza A viruses in children treated with oseltamivir: Descriptive study. The Lancet, 364, 759-765. doi:10.1016/S0140-6736(04)16934-1
Stephenson, I., et al. (2009) Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in children. Clinical Infectious Diseases, 48, 389-396. doi:10.1086/596311
Whitley, R., et al. (2001) Oral oseltamivir treatment of influenza in children. The Pediatric Infectious Disease Journal, 20, 127-133. doi:10.1097/00006454-200102000-00002
Roche (2001) Clinical trial result information (JV16284). http://www.rochetrials.com/studyResultGet.action?studyResultNumber=JV16284&productName=Tamiflu& gener ic Name=Oseltamivir
Tramontana, A.R., et al. (2010) Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerging Infectious Diseases, 16, 1068-1075. doi:10.3201/eid1607.091691
Carr, S., et al. (2011) Oseltamivir-resistant influenza A and B viruses pre- and postantiviral therapy in children and young adults with cancer. The Pediatric Infectious Disease Journal, 30, 284-288. doi:10.1097/INF.0b013e3181ff863b
Srivastava, B., et al. (2009) Host genetic background strongly influences the response to influenza A virus infections. PLoS ONE, 4, e4857. doi:10.1371/journal.pone.0004857
van der Laan, J.W., et al. (2008) Animal models in influenza vaccine testing. Expert Review of Vaccines, 7, 783-793. doi:10.1586/14760584.7.6.783
Barnard, D.L. (2009) Animal models for the study of influenza pathogenesis and therapy. Antiviral Research, 82, A110-A122. doi:10.1016/j.antiviral.2008.12.014
Sidwell, R.W., et al. (1998) Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral Research, 37, 107-120. doi:10.1016/S0166-3542(97)00065-X
Mendel, D.B., et al. (1998) Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Antimicrob Agents Chemother, 42, 640-646. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC105511/pdf/ac000640.pdf
Yen, H.L., et al. (2005) Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. Journal of Infectious Diseases, 192, 665-672. doi:10.1086/432008
Sidwell, R.W., et al. (2007) Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob Agents Chemother, 51, 845-851. doi:10.1128/AAC.01051-06
Suguitan, A.L., et al. (2006) Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets. PLOS Medicine, 3, e360. doi:10.1371/journal.pmed.0030360
Tamura, S.I. (2010) Studies on the usefulness of intranasal inactivated influenza vaccines. Vaccine, 28, 6393-6397. doi:10.1016/j.vaccine.2010.05.019
Min, J.Y., et al. (2010) Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets. Virology, 408, 128-133. doi:10.1016/j.virol.2010.09.009
Ison, M.G., et al. (2006) Comparative activities of oseltamivir and A-322278 in immunocompetent and immunocompromised murine models of influenza virus infection. Journal of Infectious Diseases, 193, 765-772. doi:10.1086/500464
Reed, L. and Muench, H. (1938) A simple method of estimating fifty percent endpoints. The American Journal of Hygiene, 27, 493-497. http://aje.oxfordjournals.org/content/27/3/493.short
Luke, T.C., et al. (2006) Meta-analysis: Convalescent blood products for spanish influenza pneumonia: A future H5N1 treatment? Annals of Internal Medicine, 145, 599. http://annals.org/article.aspx?articleid=729754
WHO (2008) Update on avian influenza A (H5N1) virus infection in humans. New England Journal of Medicine, 358, 261-273. doi.10.1056/NEJMra0707279
de Jong, M.D., et al. (2005) Oseltamivir resistance during treatment of influenza A (H5N1) infection. New England Journal of Medicine, 353, 2667-2672. doi.10.1056/NEJMoa054512
De Marco, D., et al. (2012) A non-VH1-69 heterosubtypic neutralizing human monoclonal antibody protects mice against H1N1 and H5N1 viruses. PLoS ONE, 7, e34415. doi:10.1371/journal.pone.0034415
Mozdzanowska, K., et al. (1997) A pulmonary influenza virus infection in SCID mice can be cured by treatment with hemagglutinin-specific antibodies that display very low virus-neutralizing activity in vitro. Journal of Virology, 71, 4347-4355. http://jvi.asm.org/content/71/6/4347.abstract
Prabakaran, M., et al. (2009) Combination therapy using chimeric monoclonal antibodies protects mice from lethal H5N1 infection and prevents formation of escape mutants. PLoS ONE, 4, e5672. doi:10.1371/journal.pone.0005672
Simmons, C.P., et al. (2007) Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza. PLOS Medicine, 4, e178. doi:10.1371/journal.pmed.0040178
Király, J., et al. (2011) Evaluation of anti-influenza efficiency of polyclonal IgG antibodies specific to the ectodomain of M2 protein of influenza A virus by passive immunization of mice. Acta Virologica, 55, 261-265. doi:10.4149/av_2011_03_261