Ebola virus convalescent blood products: where we are now and where we may need to go

Thierry Burnouf, Jerard Seghatchian, Thierry Burnouf, Jerard Seghatchian

Abstract

The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed,is passive immunization performed by transfusing blood, plasma or plasma immunoglobul infractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach.In countries without access to advanced blood-processing technologies, the choice may initially be restricted to convalescent whole blood or plasma. In technologically advanced countries, additional options for convalescent blood products are available, including virally inactivated plasma and fractionated immunoglobulins. The preparation of minipool immunoglobulins is also a realistic option to consider.

Figures

Fig. 1
Fig. 1
Flow-chart presenting the various technical possibilities that currently can theoretically be considered for producing convalescent blood products. Virally-inactivated plasma and immunoglobulins can also be made from recovered plasma. *unlicensed; **developed in Egypt; ***under clinical trial in immuno-deficient patients; IgG: immunoglobulin G; CF: coagulation factors; alb: albumin; S/D: solvent/detergent; S/D-F: solvent/detergent-filtered; UV: ultraviolet light; VI: virally-inactivated.

References

    1. Blajchman M.A. Protecting the blood supply from emerging pathogens: the role of pathogen inactivation. Transfus Clin Biol. 2009;16:70–74.
    1. Dodd R.Y. Emerging pathogens and their implications for the blood supply and transfusion transmitted infections. Br J Haematol. 2012;159:135–142.
    1. Breban R., Riou J., Fontanet A. Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk. Lancet. 2013;382:694–699.
    1. Wong V.W., Dai D., Wu A.K., Sung J.J. Treatment of severe acute respiratory syndrome with convalescent plasma. Hong Kong Med J. 2003;9:199–201.
    1. Kong L.K., Zhou B.P. Successful treatment of avian influenza with convalescent plasma. Hong Kong Med J. 2006;12:489.
    1. Leider J.P., Brunker P.A., Ness P.M. Convalescent transfusion for pandemic influenza: preparing blood banks for a new plasma product? Transfusion. 2010;50:1384–1398.
    1. Zingher A., Mortimer P. Convalescent whole blood, plasma and serum in the prophylaxis of measles: JAMA, 12 April, 1926; 1180–1187. Rev Med Virol. 2005;15:407–418. discussion 18–21.
    1. Luke T.C., Kilbane E.M., Jackson J.L., Hoffman S.L. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145:599–609.
    1. Gunn W. Convalescent serum in prophylaxis of measles, chicken-pox, and mumps. Br Med J. 1932;1:183–185.
    1. Anonymous . World Health Organization; Geneva: 2014. Position Paper on collection and use of convalescent plasma or serum as an element in filovirus outbreak response. WHO Blood Regulators Network (BRN). 14 August 2014.
    1. WHO . World Health Organization; Geneva: 2014. Consultation on potential Ebola therapies and vaccines- Background document for participants. 3 Sep 2014.
    1. Gulland A. First Ebola treatment is approved by WHO. Br Med J. 2014;349:g5539.
    1. Mupapa K., Massamba M., Kibadi K. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis. 1999;179(Suppl. 1):S18–S23.
    1. Emond R., Evans B., Bowen E., Lloyd G. A case of Ebola virus infection. Br Med J. 1977;2:541.
    1. Parren P.W., Geisbert T.W., Maruyama T., Jahrling P.B., Burton D.R. Pre- and postexposure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody. J Virol. 2002;76:6408–6412.
    1. Macneil A., Reed Z., Rollin P.E. Serologic cross-reactivity of human IgM and IgG antibodies to five species of Ebola virus. PLoS Negl Trop Dis. 2011;5:e1175.
    1. Takada A., Ebihara H., Feldmann H., Geisbert T.W., Kawaoka Y. Epitopes required for antibody-dependent enhancement of Ebola virus infection. J Infect Dis. 2007;196(Suppl. 2):S347–S356.
    1. Takada A., Feldmann H., Ksiazek T.G., Kawaoka Y. Antibody-dependent enhancement of Ebola virus infection. J Virol. 2003;77:7539–7544.
    1. Geisbert T.W., Hensley L.E., Geisbert J.B., Jahrling P.B. Evidence against an important role for infectivity-enhancing antibodies in Ebola virus infections. Virology. 2002;293:15–19.
    1. McGuire L.W., Redden W.R. The use of convalescent human serum in influenza pneumonia-a preliminary report. Am J Public Health. 1918;8:741–744.
    1. Parry R.P., Tettmar K.I., Hoschler K. Strategies for screening blood donors to source convalescent H1N1v plasma for intervention therapy. Vox Sang. 2012;103:107–112.
    1. Gundersen T. Convalescent blood for herpes zoster. Trans Am Ophthalmol Soc. 1935;33:508–520.
    1. Jensen C. The 1934 Epidemic of poliomyelitis in Denmark. Preliminary report on the epidemiology, clinical features and convalescent serum therapy: (section of pathology) Proc R Soc Med. 1935;28:1007–1026.
    1. Dewar H.A. Treatment of typhoid fever with convalescent whole blood. J R Army Med Corps. 1946;86:249–253.
    1. Nabarro D.N., Signy A.G. Convalescent serum in prophylaxis of measles. Br Med J. 1931;1:12–13.
    1. Avenard G., Gaiffe M., Herzog F. The prevention of chickenpox in high risk children. Comparison of the effectiveness of specific immunoglobulins and of defibrinated convalescent plasma. 414 cases (author's transl) Nouv Presse Med. 1979;8:673–675.
    1. Wong H.K., Lee C.K., Hung I.F. Practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza A (H1N1) infection. Transfusion. 2010;50:1967–1971.
    1. Maiztegui J.I., Fernandez N.J., de Damilano A.J. Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome. Lancet. 1979;2:1216–1217.
    1. Cheng Y., Wong R., Soo Y.O. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24:44–46.
    1. Mair-Jenkins J., Saavedra-Campos M., Baillie J.K. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2014 pii: jiu396.
    1. Soo Y.O., Cheng Y., Wong R. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004;10:676–678.
    1. Yeh K.M., Chiueh T.S., Siu L.K. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005;56:919–922.
    1. Hung I.F., To K.K., Lee C.K. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52:447–456.
    1. Zhou B., Zhong N., Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007;357:1450–1451.
    1. Frame J.D., Verbrugge G.P., Gill R.G., Pinneo L. The use of Lassa fever convalescent plasma in Nigeria. Trans R Soc Trop Med Hyg. 1984;78:319–324.
    1. Mohr H., Pohl U., Lambrecht B., Wieding J.U., Schmitt H. Methylene blue/light treatment of virus inactivated human plasma: production and clinical experience. Infusionsther Transfusionsmed. 1993;20(Suppl. 2):19–24.
    1. Singh Y., Sawyer L.S., Pinkoski L.S. Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function. Transfusion. 2006;46:1168–1177.
    1. Bihm D.J., Ettinger A., Buytaert-Hoefen K.A. Characterization of plasma protein activity in riboflavin and UV light-treated fresh frozen plasma during 2 years of storage at −30 degrees C. Vox Sang. 2010;98:108–115.
    1. Klein H.G. Pathogen inactivation technology: cleansing the blood supply. J Intern Med. 2005;257:224–237.
    1. Rock G. A comparison of methods of pathogen inactivation of FFP. Vox Sang. 2011;100:169–178.
    1. Solheim B.G., Seghatchian J. Update on pathogen reduction technology for therapeutic plasma: an overview. Transfus Apher Sci. 2006;35:83–90.
    1. El-Ekiaby M., Sayed M.A., Caron C. Solvent-detergent filtered (S/D-F) fresh frozen plasma and cryoprecipitate minipools prepared in a newly designed integral disposable processing bag system. Transfus Med. 2010;20:48–61.
    1. Goubran H.A., Burnouf T., Radosevich M. Virucidal heat-treatment of single plasma units: a potential approach for developing countries. Haemophilia. 2000;6:597–604.
    1. Watt G., Kantipong P., Jongsakul K., de Souza M., Burnouf T. Passive transfer of scrub typhus plasma to patients with AIDS: a descriptive clinical study. QJM. 2001;94:599–607.
    1. Watt G., Kantipong P., de Souza M. HIV-1 suppression during acute scrub-typhus infection. Lancet. 2000;356:475–479.
    1. Vittecoq D., Mattlinger B., Barre-Sinoussi F. Passive immunotherapy in AIDS: a randomized trial of serial human immunodeficiency virus-positive transfusions of plasma rich in p24 antibodies versus transfusions of seronegative plasma. J Infect Dis. 1992;165:364–368.
    1. Vittecoq D., Chevret S., Morand-Joubert L. Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma. Proc Natl Acad Sci U S A. 1995;92:1195–1199.
    1. Burnouf T., Radosevich M., El-Ekiaby M. Nanofiltration of single plasma donations: feasibility study. Vox Sang. 2003;84:111–119.
    1. El-Ekiaby M., Radosevich M., Goubran H., El Sayed M., Burnouf T. New methods of plasma fractionation – a presentation of the ‘mini-pool’ fractionation procedure developed in Egypt. ISBT Science Series. 2009;4(1):99–106. State of the Art Presentations.
    1. Dichtelmuller H., Rudnick D., Kloft M. Inactivation of lipid enveloped viruses by octanoic acid treatment of immunoglobulin solution. Biologicals. 2002;30:135–142.
    1. Korneyeva M., Hotta J., Lebing W., Rosenthal R.S., Franks L., Petteway S.R., Jr Enveloped virus inactivation by caprylate: a robust alternative to solvent-detergent treatment in plasma derived intermediates. Biologicals. 2002;30:153–162.
    1. El-Ekiaby M., Burnouf T., El-Marsafy A., Galal N., Goubran H., Radosevic M. Clinical evaluation of minipool immunoglobulin plasma fraction in primary immunodeficiency patients. 5A-S42-02. Vox Sang. 2014;107:1–56.
    1. Solheim BG, Seghatchian J. Pathogen Inactivation. In: Simon TL, Snyder EL, Solheim BG, Stowell C.P., Strauss RG, Petrides M, editors. Rossi's Principles of Transfusion Medicine. 4th ed. Wiley-Blackwell; Oxford, UK: 2009.
    1. BRN WBRN . World Health Organization; Geneva: 2014. Potential for use of convalescent plasma in management of Ebola. 14 August 2014.
    1. Burnouf T. Modern plasma fractionation. Transfus Med Rev. 2007;21:101–117.
    1. Radosevich M., Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang. 2010;98:12–28.
    1. WHO Annex 4. Recommendations for the collection, quality control and regulation of human plasma for fractionation. WHO Tech Rep Ser. 2007;941:189–264.
    1. Sabchareon A., Burnouf T., Ouattara D. Parasitological and clinical human response to immunoglobulin administration in falciparum-malaria. Am J Trop Med Hyg. 1991;45:297–308.
    1. Zhang Z., Xie Y.W., Hong J. Purification of severe acute respiratory syndrome hyperimmune globulins for intravenous injection from convalescent plasma. Transfusion. 2005;45:1160–1164.
    1. Planitzer C.B., Modrof J., Kreil T.R. West Nile virus neutralization by US plasma-derived immunoglobulin products. J Infect Dis. 2007;196:435–440.
    1. Rabel P.O., Planitzer C.B., Farcet M.R. Increasing West Nile virus antibody titres in central European plasma donors from 2006 to 2010. Euro Surveill. 2011;16
    1. Farcet M.R., Planitzer C.B., Stein O., Modrof J., Kreil T.R. Hepatitis A virus antibodies in immunoglobulin preparations. J Allergy Clin Immunol. 2010;125:198–202.
    1. Audet S., Virata-Theimer M.L., Beeler J.A. Measles-virus–neutralizing antibodies in intravenous immunoglobulins. J Infect Dis. 2006;194:781–789.
    1. Burnouf T., Emmanuel J., Mbanya D. Ebola: a call for blood transfusion strategy in sub-Saharan Africa. Lancet. 2014;384:1347–1348.
    1. WHO . World Health Organization; Geneva: 2014. Use of convalescent whole blood or plasma collected from patients recovered from Ebola Virus Disease for transfusion, as an empirical treatment during outbreaks.

Source: PubMed

3
구독하다