Immunotherapy for Infectious Diseases

70 Kunert and Katinger
remove proteins and other contaminants and minimize the concentration of aggregates
that increase the risk of anaphylactoid and other adverse reactions in recipients. Various
technologies such as heat treatment (pasteurization) or treatment with solvent/detergent
safely inactivate enveloped viruses and contribute to product safety. Nonenveloped
viral contaminants are more difficult to inactivate. Nevertheless, careful control of
plasma donations, combined with modern production technology, has established a
high degree of safety for such products even if plasma donations are included from
infected individuals.
In the last 50 years, an increasing number of diseases and patients have been treated
with immunoglobulins. Mild adverse reactions (headache, flushing, backache, and nausea)
are often associated with fast infusion rates. Only rarely are hematologic, neurologic,
or renal adverse effects seen with high doses of IVIG.
Generally, antibodies can be used in different applications for prevention, diagnosis,
or treatment of diseases. As summarized in Table 2, depending on the intended purpose,
immunoglobulins can be generated by different production systems and in different
molecular forms.
Usually the mammalian immune system is used to generate antibodies of particular
specificities. As shown in Figure 6, antigen-induced humoral immune response leads
to a predetermined spectrum of specific antibodies, which can be rescued for various
methods of in vitro production, for permanent or transient B-cell immortalization, or
for gene isolation. Once the ability to produce antibodies is preserved in an immortal
hybridoma cell line or the genes are accessible in a transiently immortalized B-celltransformed
by Epstein-Barr virus (EBV), a broad network of technologies for stable
expression can be applied (see Fig. 7 for an overview). In the following chapters these
technologies and techniques are described in more detail.
IVIG from Healthy Donors
IVIGs are used in replacement therapy in patients with primary and secondary
immunodeficiency in the prevention of bacterial infections (4). HIV-infected children
are also treated since they are immunocompromised (5). In clinical experience, these
�-globulins have proved to be powerful agents in reducing the rate of serious bacterial
infections (6). Other applications, such as after bone marrow transplantations to prevent
graft-versus-host disease, or immune thrombocytopenic purpura have been reported
(7). In addition, IVIG is now also being tested for the treatment of multiple myeloma
(8,9) and recurrent spontaneous abortion (10).
Hyperimmune Sera
Hyperimmune sera are produced from plasma donations of actively vaccinated,
reconvalescent or infected donors. They are available for prevention of disease or treatment
of various viruses and pathogens; they can help with acute diseases and can protect
patients for a limited period.
A commonly used hyperimmune serum is the anti-Rh (D) immunoglobulin administered
after Rh-D-incompatible child delivery or abortion or in circumstances that
might result in maternal exposure to fetal blood of an unknown type (11). Although the
mechanism of action is not well understood, it is believed that the anti-Rh-D
immunoglobulin interacts directly with the Rh-D antigens, thereby preventing the interaction
between the antigens and the maternal immune system. The appropriate use of