Identity of “Inhibitor” and Antibody in Extracts of Virus-Induced Rabbit Papillomas

Saline extracts of the virus-induced papillomas of domestic rabbits often contain something that inhibits or neutralizes the virus in vitro, as Shope first noted. 1 Serological studies have shown that when mixed with it the blood of rabbits carrying these papillomas also has in most instances the power to neutralize the virus in vitro. 2 Experiments were undertaken to learn whether the “inhibitor” procured from the papillomas may not be specific antiviral antibody of the sort present in the blood.

To test for “inhibitor”, 10% extracts of freshly procured papillomas were prepared by grinding in sand, suspending in saline, and centrifuging at about 4400 rpm for 20 minutes in an angle-head centrifuge. The clear supernatant fluids were then mixed in equal parts with a Berkefeld filtrate of the virus-induced growths of cottontail rabbits, containing virus of known titer, incubated 2 hours at 37°C, and rubbed into scarified areas on the skin of normal domestic rabbits according to a titration technic already described. 2

The papillomas of 13 domestic rabbits with high serum-antibody titers, as determined by virus-neutralization and complement-fixation tests, 2 , 3 all yielded large amounts of the “inhibitor”, extracts of the growths neutralizing completely or almost completely an amount of virus equal to 500 minimal infective doses. Similar growths of 6 domestic rabbits which had but little circulating antibody yielded little or none of the “inhibitor”, the extracts of these, prepared in the same way, having practically no capacity to neutralize virus.

To study further the relation between the “inhibitor” and antibody, pieces of the papillomas of 4 domestic rabbits, all produced by the same inoculum, were repeatedly removed and tested for yield of “inhibitor”, the amount of antibody in the serum of the rabbits being determined concurrently.