In the preantibiotic era, passively administered immune animal sera, or serum therapy, was the primary mode of treatment for many infectious diseases, including diphtheria, tetanus, scarlet fever, pneumococcal pneumonia, and menin-gitis caused by Neisseria meningitis and Haemophilus influezae (24). Immune sera contained specific antibodies which mediated therapeutic effects by promoting opsonization, neutraliz-ing toxins, and/or triggering complement-mediated bacterial lysis. Toxicity resulting from the systemic administration of foreign proteins was associated with serum therapy, however, and so serum therapy was abandoned when antibiotics became widely available in the 1940s.

Over the past half-century there has been relatively little interest in passive antibody therapy for bacterial and fungal infections because effective antimicrobial drugs have been available. However, several recent developments should renew interest in the use of passive antibody therapy alone or in combination with antimicrobial drugs. First, the emergence of antimicrobial resistance has decreased the efficacy and predictability of antimicrobial chemotherapy. Second, the difficulties of treating infections in immunocompromised individuals, particularly those with AIDS, have revealed the limitations of antimicrobial chemotherapy in the absence of effective immu-nity. Third, the hybridoma technology introduced in 1975 by Kohler and Milstein (68) provides the means of generating an unlimited supply of homogeneous monoclonal antibodies (MAbs). Technology is now available to reduce the immunogenicity of rodent MAbs in humans by constructing mouse-human chimeric or humanized MAbs (77) or to generate completely human MAbs from either hybridomas or combina-torial libraries (65). Thus, antibody-based therapies no longer depend on heterologous immune sera, with their inherent variations and toxicities, and antibodies can again be consid-ered therapeutic alternatives for a variety of infections. Potentially useful antibodies for the prevention and therapy of infectious diseases are usually identified bydemonstrating that they can modify the course of experimental infection. The choice of an animal model for use in the testing of antibody reagents can be a critical decision for demonstrating efficacy. The development of serum therapy in the preantibiotic era relied almost exclusively on animal models in the preclinical testing phase. Herewe review serum therapy for pneumococcal and meningococcal infections, with emphasis on the role of the animal models used in their development.