IMMUNITY IN MUMPS : I. EXPERIMENTS WITH MONKEYS (MACACUS MULATTA). THE DEVELOPMENT OF COMPLEMENT-FIXING ANTIBODY FOLLOWING INFECTION AND EXPERIMENTS ON IMMUNIZATION BY MEANS OF INACTIVATED VIRUS AND CONVALESCENT HUMAN SERUM.
Since the experimental data have already been discussed at some length, it is here necessary only to review those observations which appear to be of most significance. The manifestations of the disease we have produced in monkeys have in general been similar to those described by previous workers. It has been found that members of the species M. mulatta are regularly susceptible to infection with the virus of mumps, provided they have not been in contact with animals which have recently been infected. Such contact may be followed by the development of resistance to inoculation unattended by overt signs of infection. Following the intraparotid injection of virus into a susceptible animal, an antigen appears in the gland which reacts specifically in the complement fixation test with sera of monkeys which have recovered from an attack of mumps. This antigen has not been demonstrated in any other organ of the infected monkey which has been examined, nor does it persist or increase in amount when introduced into the brain or the testes. Attempts to propagate it in the tissues of other animal species including the developing hen's egg and tissue cultures have so far been uniformly unsuccessful. The antigen is relatively thermostabile, resisting a temperature of 65 degrees C. for at least 20 minutes at the optimal hydrogen ion concentration. It is unimpaired by a concentration of formalin of 0.3 per cent. Together with the virus it may be preserved indefinitely in the frozen state. The maximal quantity of antigen in the gland, which may be considerable, is attained on or about the 5th day following inoculation of the virus. An antibody which reacts with the antigen appears in the serum from 8 to 14 days after infection. This antibody has not been found in the serum of normal monkeys which have had no opportunity for contact with the virus. It has been demonstrated during convalescence in the serum of all animals which have been examined. The antibody which is present in large amounts soon after recovery, although decreasing in concentration with the lapse of time, may continue to be present for many months. At 62 degrees C. for 20 minutes its activity is not reduced and on storage at 4 degrees C. its titer has remained unaltered for over 2 years. A similar factor which appears in human beings convalescent from mumps is less stabile, since its activity is reduced appreciably under these conditions. In the CO(2) cabinet, however, both antibodies can be preserved for long periods of time. The definition of these reagents has afforded means whereby the simian infection with the virus of mumps, whether it is actively in progress or has occurred at some time in the past, can be recognized. Upon the establishment of these facts, the estimation of the quantity of antigen in the glands of vaccinated animals was employed as an index of their resistance in studies on the effect of the injection of formolized and alumprecipitated formolized suspensions of infected parotid gland. It has been shown that such vaccines, in which the virus has been rendered inactive, lead to the production of complement-fixing antibody. In about 60 per cent of the vaccinated animals, moreover, evidence of increased resistance was obtained as indicated by the partial or complete suppression of the formation of antigen in the inoculated gland. In certain instances no evidence of resistance was observed, yet antibody was found to be present. It is clear, therefore, that resistance is not determined solely by the presence of the complement-fixing antibody. The possibility, however, of its participation as a factor in immunity cannot be excluded. Employing the same criterion of resistance, the virus-neutralizing capacity of a pool of human mumps convalescent sera and of a globulin concentrate prepared from the pool has been studied. Neither of these materials was found to prevent entirely the formation of antigen, although each of them appeared to exert some inhibitory effect.
Enders
J F
JF
Department of Bacteriology and Immunology, Harvard Medical School and School of Public Health, Boston.
Kane
L W
LW
Cohen
S
S
Levens
J H
JH