Download Antibodies from Reconvalescent Donors for the Prevention and

Antibodies from Reconvalescent Donors for the
Prevention and Treatment of Virus Infections:
REVISITING AN OLD CONCEPT IN LIGHT OF THE
CURRENT EBOLA VIRUS EPIDEMIC
BY THOMAS R. KREIL, Ph.D.
Some clinical evidence suggests that
antibodies from reconvalescent donors
(persons who have recovered from infection)
may be effective in the treatment of Ebola
virus infections. Different approaches of
how to prepare such antibodies for
administration to Ebola virus-infected
patients while preventing the transmission
of other human-pathogenic viruses are
discussed here, with more detail available
to the interested reader elsewhere1.
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THE SOURCE | SPRING 2015
Antibodies from reconvalescent donors, at the time from
horses, have been used for the treatment of infectious
diseases for little more than one hundred years now, an
approach initially pioneered by Emil von Behring and
sufficiently impactful to earn him the first Nobel Prize
in Medicine. Over time though, driven by the advent of
vaccines and antibiotics, this treatment modality has lost
some importance, and its current use is limited to primarily
niche applications such as antivenoms/antitoxins, and few
licensed hyperimmune indications such as for example
anti-hepatitis B, or anti-rabies. And while the conceptual
value of reconvalescent antibody-based products for the
treatment of emerging viruses, such as recently West Nile
Virus or pandemic influenza viruses, has been recognized,
the required amount of pre- and clinical investigations
may have been an insurmountable obstacle to bringing the
interventions to use. The situation may be different with
the current Ebola virus (EBOV) outbreak in West Africa, in
that the scale of human suffering and death combined with
the very limited alternative options, i.e. only early stage
development products, may make any alternative that
could be more immediately available and reasonably
promising more desirable. To be respectful of scientific
evidence, the effectiveness of treating EBOV infections
with antibodies from reconvalescent donors is not fully
proven either, but some limited clinical experience can be
interpreted as encouraging, and more recent results from
preclinical work also supports the potential utility of
the approach.
Beyond the confirmation of efficacy though, concerns
all too familiar for the plasma products industry need to be
addressed: first and foremost, it is critical to prevent the
transmission of other infectious agents that may be harbored
by the donors; and secondly, the number of treatment
courses that can be made available needs to be reasonably
commensurate with the size of the challenge, to allow for
broad scale treatment of potentially all those in need, rather
than currently only the treatment of foreign aid workers who
have risked their lives in a laudable humanitarian effort.
To address the safety aspects, history has proven that
testing the donations will be an imperfect solution. Despite
the implementation of even elaborate nucleic acid test
(NAT) algorithms, non-virus inactivated transfusable blood
components still occasionally transmit West Nile Virus in
the U.S., and similar situations need to be expected in West
Africa—with an HIV-positivity rate in the adult population
of approx. 1 percent as reported by UNICEF (United Nations
Children’s Fund.) (http://www.unicef.org/infobycountry).
The transfer of EBOV antibodies, however, only requires
the transfusion of serum or plasma, a component that can
be virus-inactivated by a number of proven methods, with
the solvent-detergent treatment probably the most effective
choice for lipid-enveloped viruses as demonstrated by a
PPTA-facilitated industry collaboration2 . In one specific
embodiment, the production of solvent-detergent plasma
was achieved by use of a commercially available disposable
set of bags developed for use in a resource-limited
blood bank setting3. Against this background it is rather
disappointing to see that the World Health Organization
(WHO) guidance document4 on the use of reconvalescent
plasma for the treatment of EBOV has stopped short of
even mentioning the option of virus inactivation. Instead,
it requires the comprehensive testing of donors within 48
hours before transfusion, or for longer periods a complete
repeat, which represents quite a technical and logistical
effort to achieve a result of limited value.
For the volume aspect, it is not too difficult to
imagine how a basic plasmapheresis infrastructure could
be established in West Africa, once the hospital-like
infrastructure committed by several countries is
available there.
All-in-all, it seems that the use of antibodies from
reconvalescent donors may find yet another medical use, and
with the support pledged by large philanthropic entities the
scientific support for the currently to some degree assumed
efficacy is expected to improve soon. For the necessary
safety and volume considerations it could have been more
effective to also involve the expertise of the plasma products
industry, ideally under the auspices of WHO so that its
guidance on the use of reconvalescent plasma could have
been more comprehensive: the experience this industry
has accumulated in both pathogen safety issues as well
as volume challenges, could have helped accelerating the
availability of a quite possibly helpful intervention in one of
the most dire recent infectious disease outbreaks.
THOMAS R. KREIL, Ph.D., Associate Professor of Virology,
Senior Director, Global Pathogen Safety, Baxter BioScience
References
1
Kreil TR. Treatment of Ebola virus infection with antibodies from
reconvalescent donors. Emerg Infect Dis. 2015 Mar;21(3):521-3
http://dx.doi.org/10.3201/eid2103.141838
2
Dichtelmüller HO, Biesert L, Fabbrizzi F, Gajardo R, Gröner A, von Hoegen I,
Jorquera JI, Kempf C, Kreil TR, Pifat D, Osheroff W, Poelsler G. Robustness
of solvent/detergent treatment of plasma derivatives: a data collection from
Plasma Protein Therapeutics Association member companies. Transfusion
2009;49(9):1931-43.
3
El-Ekiaby M, Sayed MA, Caron C, Burnouf S, El-Sharkawy N, Goubran H,
Radosevich M, Goudemand J, Blum D, de Melo L, Soulié V, Adam J, Burnouf
T. Solvent-detergent filtered (SD-F) fresh frozen plasma and cryoprecipitate
minipools prepared in a newly designed integral disposable processing bag
system. Transf Med 2010;20:48–61
4
Use of Convalescent Whole Blood or Plasma Collected from Patients
Recovered from Ebola Virus Disease for Transfusion, as an Empirical
Treatment during Outbreaks. Interim Guidance for National Health
Authorities and Blood Transfusion Services Version 1.0 September 2014;
accessed at http://apps.who.int/iris/bitstream/10665/135591/1/WHO_HIS_
SDS_2014.8_eng.pdf
SPRING 2015 | THE SOURCE
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