Serial specimens of human serum were studied for the presence of anti-virus antibodies following the intentional inoculation of viruses as part of a clinical experimental study of the effects of these virus infections upon advanced cancer. Included in the study are sera from 20 patients following the inoculation of Smithburn's isolate of West Nile virus, and 50 patients following inoculation of the Egypt 101 isolate of West Nile virus; 20 patients following Ilhéus virus, 10 patients following Newcastle disease virus, and 1 or more patients following inoculation of Bunyamwera, Semliki Forest, Br I, Rabies, and R viruses, and the Egypt 19 and Egypt 21 isolates of West Nile virus. Almost all sera were studied by complement fixation technique, and many were studied by neutralization techniques. Sera from 3 patients were also studied for anti-hemagglutinating antibodies against West Nile virus.

All of the techniques included in this study appeared to be approximately equivalent in their capacity to detect and quantitate antibody formation. In general, these viruses caused production of detectable antibodies in a majority of patients between 3 and 4 weeks after virus inoculation. Thereafter neutralizing antibody titers remained generally stable for the duration of this study, which rarely exceeded 6 months, but complement-fixation antibody titers often fell after 3 to 4 months. Newcastle disease virus differend from the other viruses studied in that the onset of complement-fixing antibody formation was more rapid and the titer of serum antibodies was greater than seen with the other viruses studied. This difference, however, was not observed when the neutralization technique was used.

These data are in agreement with the conclusion that Egypt 101 virus and West Nile virus are antigenically identical, and data from a single patient is compatible with the view that Egypt 21 virus is also identical with West Nile virus. No satisfactory data were available for any conclusion concerning the Egypt 19 virus. There was no major cross-reaction between the West Nile viruses and Ilhéus virus. Antibodies against Japanese encephalitis virus were demonstrated in 2 patients following inoculation of Egypt 101 and Ilhéus virus. These same sera did not react with Western equine encephalitis virus.

There were no data which suggested that any of the patients included in this study had had any previous exposure to West Nile or any antigenically similar virus. A few patients showed suggestive, but not conclusive, evidence of previous contact with antigenic material similar to Ilhéus and Newcastle disease viruses.

Antibody formation occurred following inoculation of virus whether the virus propagated or not. Among patients inoculated with a single virus, there was no apparent correlation between the amount of virus propagation and the magnitude of the antibody response. However, when comparing different viruses, it appeared that those viruses which were more infective for man also stimulated greater antibody production. There were suggestive data to indicate that antibody formation in patients with lymphomatous neoplasms is poorer than in patients with other types of neoplastic disease. There was no apparent relationship between antibody forming ability and various types of cancer other than lymphoma.

1

This work was supported in part by grants from The American Cancer Society, the Damon Runyon Fund for Cancer Research, and the National Cancer Institute of the U. S. Public Health Service.

2

The authors wish to acknowledge their indebtedness to Judith D. Epstein and David T. Mount for technical assistance.

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