PROPHYLAXIS AND THERAPY OF INFLUENZA PNEUMONIA IN MICE BY INTRATRACHEAL INSTILLATION OF MONOCLONAL ANTIBODY
Abstract
This study on passive immunity dealt principally with the following topics: pathogenesis of the pneumonia produced by influenza virus (PR8) in CF-1 mice; the distribution and retention of monoclonal antibody instilled intratracheally (IT) into the lung; and prophylaxis and therapy of influenza pneumonia using specific monoclonal antibody (IgG 2a/k anti-HA). The pathogenesis of influenza pneumonia in CF-1 mice was investigated with respect to: recovery of virus and its localization in the lungs; gross and histopathologic changes; loss of body weight; and lethality. The percent body weight lost by day 3 was shown to be a reliable predictor of mortality and was used to define the degree of clinical illness. The fate of a single 50 ul bolus of antibody instilled IT was determined by monitoring the activity of ('125)I-labelled monoclonal IgG in the lungs and by lavage recovery of functional antibody. Antibody was demonstrated in high concentrations for the first 3 days and was present in the lungs for a period of 7 days. For prophylaxis several trials indicated that monoclonal antibody provided significant protection from lethal effects of the virus. At 3 and 7 days following IT there were no deaths from virus challenge, and only minimal lesions developed in the lungs. At 10 days there were some deaths, but there was still significant protection (P < 0.001). At 14 days there was reduced mortality compared to the controls, but it was not significant. In therapeutic experiments a significant reduction in mortality occurred following a single IT treatment at 1, 2, 3, or 4 days following inoculation of virus. Treatment at 1 day aborted the infection so that lesions did not develop in most mice. Antibody given to clinically ill mice on day 3 produced a highly significant reduction in mortality (P < 0.001) when compared to control mice. The treatment reversed the weight loss and apparently arrested the development of lesions in most of the mice within 2 days following antibody administration.
Degree
Ph.D.
Subject Area
Immunology
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