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Prevention of 334C Murine Virus-induced Leukemia by Transmission of Maternal Immunity to Offspring¹

Department of Medical Viral Oncology, Roswell Park Memorial Institute, Buffalo, New York 14203, and Graduate Faculty in Microbiology, State University of New York at Buffalo (Roswell Park Division), Buffalo, New York 14214

Mice were protected against development of virus-induced leukemia late in life when they were suckled on female mice immunized as adults with 334C murine leukemia virus, a member of the Friend-Moloney-Rauscher subgroup of murine leukemia viruses. Young adult, random-bred Ha/ICR Swiss females were immunized with one to three injections of virus filtrate from organs of leukemic mice at weekly intervals and were mated during or after immunization. Offspring were challenged at birth by injection with 334C virus and then suckled on immunized females until weaned. The incidence of leukemia was reduced to an average of 10% in offspring from immunized females, compared to an average of 72% in offspring from nonimmunized females. The capability of virus-immunized females to protect their young extended over a period of 5 to 6 months.

Neonatal mice also were protected against development of leukemia when they were suckled on virus-immunized females either before or after infection by vertically transmitted 334C virus in reciprocal foster nursing experiments. Offspring were suckled on virus-immunized mothers for 2, 8, and 14 days before being transferred to virus-infected females. Leukemia developed in 36, 15, and 14% of offspring, as compared with 71, 38, and 7% in control litters (offspring from nonimmunized mothers suckled on virus-infected females). When offspring were suckled on virus-infected mothers for 2, 8, and 14 days before being transferred for suckling to virus-immunized females, leukemia developed in 6, 33, and 81% as compared with 83, 68, and 72% in control litters (virus-infected offspring suckled on normal females).

The results of these experiments define a critical period, early in life, during which the course of virus infection can be altered and the incidence of leukemia in adult life greatly influenced. Thus, this murine system provides a model for exploration of the application of combined immunotherapy and antiviral chemotherapy to the prevention of virus-induced leukemia.

¹ Supported in part by grants from the John A. Hartford Foundation and USPHS Grant CA-07745.

Received 8/ 2/73. Accepted 12/ 7/73.