The Effect of Nutritional Deficiencies on the Development of Neutralizing Antibodies and Associated Changes in Cerebral Resistance against the Virus of Western Equine Encephalomyelitis

Abstract

Summary The influence of underfeeding, deficiency of the whole “B” complex, thiamin-deficiency, riboflavin-deficiency, carbohydrate-deficiency and protein-deficiency was studied with respect to its effect on the development of immunity in mice vaccinated with formalinized Western equine encephalomyelitis mouse brain virus. Immunity was determined by the development of cerebral resistance and of neutralizing antibodies. The latter were quantitatively determined by the method of serum dilution as well as the usual method employing undiluted serum. Mice were given three doses of vaccine of 0.3 ml each intraperitoneally on three alternate days and were tested two weeks after the first dose. Underfed mice developed considerable immunity but not to the same extent as did those on an adequate diet. The well-nourished vaccinated mice resisted between 100 and 200 times more virus intracerebrally than did the underfed animals. The test for neutralizing antibodies likewise showed a significant difference between undernourished and well-nourished mice, with the well-nourished animals neutralizing between 10 and 100 times as much virus as did the starved mice. The serum of the adequately nourished animals could be diluted between 3 and 8 times more than that of the serum obtained from the undernourished mice and still neutralize the effects of a constant amount of virus (50 LD50 doses). Prolonging the period of starvation for an additional two weeks did not accentuate the depressed immunity response. There was no difference in the immune response of animals on a synthetic diet and those on a stock diet. Removal of the whole “B” complex from the synthetic diet yielded equivocal results regarding the immune response in mice, but a decreased ability on the part of “B”-deficient animals to produce antibodies appeared possible. In one case the “B”-deficient animals developed a neutralization index which was 15 fold less than that of the control animals and no difference when the diluted serum was tested against a constant amount of virus and in the other case no difference between neutralization indexes occurred but this time the serum from adequately fed animals could be diluted six times more than that of the “B”-deficient animals and still neutralize the effects of a constant amount of virus. Thiamin- or riboflavin-deficiency had no effect either on the production of neutralizing antibodies or on the development of cerebral resistance. Protein- or carbohydrate-deficiency did not cause a marked failure on the part of deficient animals to develop immunity but there was a quantitative difference. The cerebral immunity was about ten fold greater in the well-nourished than in the deficient mice. The neutralization index of the serum from the well-nourished animals was twenty fold greater and the serum could be diluted three to four times more and still neutralize the effect of 50 LD50 doses of virus in mice.