Health  Vol.4 No.10 A , October 2012
Antibody administration in experimental influenza increases survival and enhances the effect of oseltamivir
Abstract: 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.
Cite this paper: Pourroy, B. , Kolmos, H. and Nielsen, L. (2012) Antibody administration in experimental influenza increases survival and enhances the effect of oseltamivir. Health, 4, 933-940. doi: 10.4236/health.2012.430143.

[1]   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

[2]   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

[3]   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

[4]   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

[5]   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

[6]   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

[7]   Kong, L. and Zhou, B. (2006) Successful treatment of avian influenza with convalescent plasma. Hong Kong Medical Journal, 12, 489.

[8]   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

[9]   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

[10]   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

[11]   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

[12]   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

[13]   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

[14]   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

[15]   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

[16]   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

[17]   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

[18]   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

[19]   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

[20]   Ekiert, D.C., et al. (2009) Antibody recognition of a highly conserved influenza virus epitope. Science, 324, 246-251. doi:10.1126/science.1171491

[21]   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

[22]   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

[23]   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

[24]   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

[25]   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

[26]   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

[27]   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

[28]   Roche (2001) Clinical trial result information (JV16284). gener ic Name=Oseltamivir

[29]   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

[30]   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

[31]   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

[32]   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

[33]   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

[34]   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

[35]   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.

[36]   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

[37]   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

[38]   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

[39]   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

[40]   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

[41]   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

[42]   Reed, L. and Muench, H. (1938) A simple method of estimating fifty percent endpoints. The American Journal of Hygiene, 27, 493-497.

[43]   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.

[44]   WHO (2008) Update on avian influenza A (H5N1) virus infection in humans. New England Journal of Medicine, 358, 261-273. doi.10.1056/NEJMra0707279

[45]   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

[46]   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

[47]   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.

[48]   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

[49]   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

[50]   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