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

Arturo Casadevall

Disclosures

Emerging Infectious Diseases. 2002;8(8) 

In This Article

Abstract and Introduction

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host's ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats.

Defense strategies against biological weapons include such measures as enhanced epidemiologic surveillance, vaccination, and use of antimicrobial agents, with the important caveat that the final line of defense is the immune system of the exposed individual. The potential threat of biological warfare and bioterrorism is inversely proportional to the number of immune persons in the targeted population. Thus, biological agents are potential weapons only against populations with a substantial proportion of susceptible persons. For example, smallpox virus would not be considered a useful biological weapon against a population universally immunized with vaccinia.

Vaccination can reduce the susceptibility of a population against specific threats provided that a safe vaccine exists that can induce a protective response. Unfortunately, inducing a protective response by vaccination may take longer than the time between exposure and onset of disease. Moreover, many vaccines require multiple doses to achieve a protective immune response, which would limit their usefulness in an emergency vaccination program to provide rapid prophylaxis after an attack. In fact, not all vaccine recipients mount a protective response, even after receiving the recommended immunization schedule. Persons with impaired immunity are often unable to generate effective response to vaccination, and certain vaccines may be contraindicated for them.[1] For example, the vaccine against hepatitis B does not elicit an antibody response in approximately 10% of vaccines, and the percentage of nonresponders is substantially higher in immunocompromised persons.[1]

Drugs can provide protection when administered after exposure to certain agents, but none are available against many potential agents of biological warfare. Currently, no small-molecule drugs are available that prevent disease following exposure to preformed toxins. The only currently available intervention that could provide a state of immediate immunity is passive immunization with protective antibody. Passive antibody therapy was widely used in the pre-antibiotic era but was largely abandoned with the advent of antimicrobial chemotherapy.[2,3] In recent years, there has been a renaissance in the use of antibodies for therapy: 10 monoclonal antibodies (MAbs) are currently licensed and dozens are in the developmental pipeline.[4] This article reviews the activity of humoral immunity against several biological agents, discusses the advantages and disadvantages of an antibody-based defense strategy ( Table ), and proposes stockpiling specific antibodies for use in the event of biological attacks.

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