SIMPLIFIED PRODUCTION OF ANTIMENINGOCOCCIC SERUM.
In an attempt to simplify the manufacture of an efficacious antimeningococcus serum an experimental study has been made of a number of sera produced with a few or with single strains of meningococcus, the therapeutic polyvalent serum produced at The Rockefeller Institute with more than 50 strains being used as a standard of comparison. It was found that horses injected with an antigen limited to five, three, or even one strain yielded sera with a range of agglutinins covering in high dilution practically all the stock strains used in producing the polyvalent serum. These sera appeared to equal the polyvalent serum in range and titer of agglutinins, but on further examination fundamental differences were found. Storage for a year had little effect upon the titer and inclusiveness of the polyvalent serum, whereas the monovalent serum had fallen off greatly, especially in regard to secondary or subsidiary agglutinins, so that only a comparatively small number of stock strains was still agglutinated. The serum made with five strains, a regular, a para, and three intermediate meningococci, approached the polyvalent serum in keeping qualities and still agglutinated at the end of this period 39 of the 41 strains tested. Absorption tests also brought out inherent differences in the nature of the polyvalent and the monovalent sera which had appeared to be practically identical in simple agglutination tests. The homologous strain on triple absorption was able to exhaust the monovalent serum completely, but was unable to remove from the polyvalent serum agglutinins to which 30 of 44 different strains were able to react. Absorption with another single strain of the same type removed from the monovalent serum agglutinins for a majority of the test strains but left the polyvalent serum relatively unaffected. It is comparatively easy to produce a serum effective against about 80 per cent of the spinal strains of meningococci encountered. Deficiencies in our knowledge of the antigenic capacities of the meningococcus have led to the more or less empirical use of a large number of cultures in the preparation of a serum effective against the remaining 20 per cent of the strains. How far the number of the latter in the antigen may be reduced without restricting the efficacy of the serum remains yet to be determined. However, the experimental evidence recorded here apparently does not favor the use of an antigen limited to one or too few strains. For example, three or five selected strains produced a serum which agglutinated practically all the strains against which it was tested. But in view of the many observations which point to the greater therapeutic efficacy of a serum made with a larger number of strains we would not as yet advocate a serum prepared with too limited antigens even though it contains at first a wide range of agglutinins. It has been brought out that a monovalent serum contains, in addition .to specific agglutinins, a wide range of common or secondary agglutinins which tend to disappear during storage. The difference between specific and secondary agglutinins is not apparent in simple agglutination tests, but is revealed by absorption tests. It is probable that in a serum prepared with a few strains the same condition exists, whereas in a serum produced with a large number of strains the agglutinins are mainly specific as contrasted with the fact that most of them are secondary in the serum produced with few strains. The question whether secondary agglutinins are therapeutically equivalent to primary or specific agglutinins requires further study.
Laboratories of The Rockefeller Institute for Medical Research.
H L
HL
Amoss
F L
FL
Gates
P K
PK
Olitsky