Immunotherapy for Infectious Diseases

Production of Igs and MAbs Targeting Infectious Diseases 69
Fig. 5. mRNA of variable regions and corresponding polypeptides vH and vL. mRNAs of
antibodies are composed of V-(D)-J regions. These are translated as vH and vL, characterized
by relatively conserved FR regions and antigen-binding complementary determing regions
(CDRs).
Table 1
Generation of Immunoglobulin Diversity by Independent Mechanisms
Multiple germline V, D, and J genes
Different V-J light chain and V-D-J heavy chain recombinations
Recombinational inaccuracies
Somatic point mutations
Assorted heavy and light chains
resulting antibody assortment through the combination of heavy and light chains,
somatic point mutations, and recombinational accuracy. Table 1 summarizes these five
mechanisms that allow the generation of a repertoire of at least 10 8 different antibodies,
sufficient to recognize most antigens invading the body. Modern DNA recombination
technologies learned to copy these naturally occurring principles for the design of
artificial antibody molecules.
IN VIVO APPLICATION OF ANTIBODIES
Immunoglobulins for Therapeutic Applications
Immunoglobulins in the form of injectable polyclonal gammaglobulins, so-called
intramuscular immunoglobulin (IMIG) and intravenous immunoglobulin (IVIG) preparations,
have been used since 1944. In IVIG preparations, antibody oligomers must be
elimimated, to avoid spontaneous complement activation. The associated side effects
(adverse reactions) of the first generation of serotherapy were overcome by Cohn fractionation
technology (3). IVIG is prepared from pools of serum collected from large
numbers of healthy donors. Cohn-Oncley cold ethanol fractionation is based on the
principle that proteins can specifically precipitate in a certain environment, according
to size, charge, and other physicochemical properties. This technology is used by several
manufacturers to separate the �-globulin fraction from other serum proteins. Subsequent
biochemical steps downstream of the Cohn fraction are applied and may
include ion exchange chromatography, ultrafiltration, enzymatic digestion, manipulation
of pH, and salt concentration; these vary with the manufacturer. These procedures