Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

Arturo Casadevall

Disclosures

Emerging Infectious Diseases. 2002;8(8) 

In This Article

Advantages of an Antibody-Based Defense Strategy

The above summary indicates that specific antibody can be effective against some of the major biological warfare agents. In fact, antibody preparations in the form of serum therapy were used historically for the treatment of anthrax,[13] tularemia,[49] and plague,[37] albeit in uncontrolled trials that do not meet modern standards for establishing efficacy. The major advantage of passive antibody immunization in defense against biological weapons is that it provides a state of immediate immunity that can last for weeks and possibly months. Some human IgG isotypes have serum half-lives in excess of 30 days,[74] which would confer long-lived protection to passively immunized persons. Antibodies are natural products with minimal toxicity, provided that they contain no aggregates and have no reactivity with host tissues. If vaccines are available, simultaneous administration of vaccine and antibody may be possible to provide both immediate and long-lasting protection, as is done for rabies in postexposure prophylaxis. Antibodies conjugated to enzymes, radionucleotides, or drugs could provide additional antimicrobial activities apart from those conferred by the native immunoglobulin molecule.

Although passive antibody will generally have to be given systemically, oral administration can be useful against certain gastrointestinal agents. With the exception of rabies antiserum, most antibody preparations in clinical use are given intravenously. The need for intravenous administration is a severe constraint for mass passive immunization and would likely limit this practice to a few recipients. However, this disadvantage may potentially be circumvented because Ig preparations can theoretically be administered intramuscularly. Hence, generating antibody preparations suitable for delivery into one of the large muscles of the arm or leg may be possible without the need for logistically complicated intravenous infusions. Such antibody preparations could be supplied in self-injectable devices that could allow susceptible persons to protect themselves upon notification of a biological attack. However, for this scenario to be realistic, antibody preparations with high specific activity would have to be developed that would allow administration in a small volume.

An antibody-based defense strategy against biological warfare agents can be supported by a mature technology. Antibody-based therapies were first used in the late 19th century, and more than 100 years of experience has been gained in the development of therapeutic antibodies. In the past, antibody-based therapies were dependent on immune serum that was limited in availability and was associated with substantial side effects when the serum originated from animals.[2,3] In recent years, major technical advances in the ability to generate antibodies include the development of a variety of expression systems, including hybridoma, bacteria, and phage systems.[75,76] Since 1997, eight MAbs have been licensed for human therapeutic use; three of these are mouse-human chimerics and five are humanized murine MAbs.[4] Each of these molecules has been the product of advances in biotechnology, and their success supports the view that the technology is in place for implementing an antibody-based defense strategy.

Immunoglobulins are highly versatile effector molecules that can be adapted for use against virtually any infectious agent or toxin. In fact, antibody therapy is now available for a variety of situations in which natural antibody immunity is not likely to be effective, including prevention of re-stenosis after coronary angioplasty and the therapy for venomous animal bites, digitalis toxicity, breast cancer, and Crohn disease (reviewed in[77]). Furthermore, the fact that natural protection to a given pathogen may rely on cell-mediated immunity does not negate the fact that passive antibody can still mediate protection. For example, protective MAbs have now been identified against such intracellular pathogens as Ehrlichia chaffeensis,[78]Cryptococcus neoformans,[79]Listeria monocytogenes,[80]Candida albicans,[81] and Mycobacterium tuberculosis,[82] for which cell-mediated immunity is critically important for protection.

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