ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis.

Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP-ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine.

Colostrum production by ewes and the amounts ingested by lambs.

Studies involving 49 ewes which were well nourished during the last eight weeks of pregnancy indicated that ewe weight loss during pregnancy and lamb birth weights followed the recognised pattern and were within acceptable "normal" limits. Colostrum production ranged from 1238 to 4593 g per ewe during the 48 h following the first suckling and there was evidence that production levels were related to demand by the lambs. Colostrum consumption by individual lambs was related to litter size. The smaller the litter size the greater was the amount ingested during the first 48 h of life. No clear relationship was established between the amount of colostrum consumed and the level of immunoglobulin in a lamb's circulation. Possible reasons for this are discussed.

Immunoglobulin levels in ewe colostrum and in lamb serum.

The immunoglobulin content of ewe colostrum falls rapidly after the first suckling and reaches a low level 36 h after the first feed. The whey content of colostrum will rise by more than 50 per cent during the same period. The production of colostral immunoglobulin during the 24 h following the first feed was related, in this work, to the amount of colostrum produced; the greater the colostrum production, the greater the immunoglobulin production. Colostrum production ranged from 1216 to 4493 g and immunoglobulin production from 22-21 to 86-34 g during the eight feeds studied. Colostrum production was related to demand by the lambs. There was a clear positive correlation between the total amount of immunoglobulin the lambs' circulation 30 h after the first feed and the immunoglobulin consumed. Approximately 20 to 25 per cent of the immunoglobulin ingested was present in the lambs' circulation at this time.