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

Arturo Casadevall

Disclosures

Emerging Infectious Diseases. 2002;8(8) 

In This Article

Polyclonal Versus MAb Products

In common usage, the term polyclonal antibody preparation refers to immune sera that usually contain pathogen-specific antibodies of various isotypes and specificities. In contrast, MAb preparations consist of a single immunoglobulin type, representing one isotype with one specificity. In theory, polyclonal preparations for human therapeutic use can be generated by mixing MAbs. Each product has important advantages and disadvantages that must be weighed in considering the development of a passive antibody strategy.

Polyclonal preparations have the advantage of consisting of diverse immunoglobulins that target different antigens; the heterogeneity in isotype composition confers broader biological activity through the various constant regions. Polyclonal preparations are generally relatively easy to make, provided that immune donors are available. However, the amount of specific antibodies in a polyclonal preparation usually represents only a minute fraction of the total antibody protein. Hence, polyclonal preparations tend to have low specific activity relative to MAb preparations. For example, in a comparison of the activity of human MAbs with that of human immune globulin, 0.7 mg of a mixture of two MAbs had the same neutralizing activity as 100 mg-170 mg of tetanus immune globulin.[90] Other problems associated with polyclonal preparations generated from immune donors are lot-to-lot variations in the amount of specific antibody,[91] limited supply,[92] and the possibility of transmission of infectious agents.[93]

MAbs have the advantage that they can be defined precisely with regard to structure, specificity and activity. Furthermore, MAbs produced in vitro by hybridomas or other expression systems can provide an inexhaustible supply of immunoglobulin, thus freeing production from relying on a limited number of immune donors. However, the fact that MAbs recognize only a single epitope means that they have limited usefulness against pathogens that exhibit antigenic variation. This problem can be circumvented by generating MAb cocktails, with the caveat that such preparations would likely encounter a more complex regulatory process.

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