Vaccines are either “autogenous” or “stock.” An “autogenous” vaccine is a vaccine that is made from bacteria derived from the individual or animal which it is desired to vaccinate and contains not only the particular organism but the particular strain of that organism which is responsible for the lesion. Stock vaccines are made up from organisms like the infective agent in a given case but derived from some other person or animal or from laboratory cultures. Commercial vaccines are “stock” vaccines and are usually “polyvalent” or even “mixed.” A “polyvalent” vaccine contains several strains of the infective agent and a “mixed” contains several different organisms.
Stock vaccines have shown their value when used as preventive inoculations, notably so in typhoid fever in man, anthrax and black-leg in cattle. The author is strongly of the opinion, not only from the extended literature on the subject, but also from his own experience in animal, and especially in human cases, that stock vaccines are much inferior and much more uncertain in their action when used in the treatment of an infection, than are autogenous vaccines. This applies particularly to those instances in which pneumococci, streptococci, micrococci, and colon bacilli are the causative agents but to others as well. The following are some of the reasons for this opinion: The above organisms are notoriously extremely variable in their virulence. While there is no necessarily close connection between virulence and antigenic property, yet since virulence is so variable, it is rational to assume that antigenic property is also extremely variable. Individuals vary just as much in susceptibility and hence in reactive power, and generally speaking, an individual will react better in the production of antibodies to a stimulus to which he has been more or less subjected, i.e., to organisms derived from his own body.
In the preparation of a vaccine great care must be used in heating so that the organisms are killed, but the antigens are not destroyed. Many of the enzymes present in bacteria, especially the proteolytic ones, are not any more sensitive to heat than are the antigens, hence are not destroyed entirely. Therefore a vaccine kept in stock for a long time gradually has some of its antigens destroyed by the uninjured enzymes present with them, and so loses in potency. Therefore in treating a given infection it is well to make up a vaccine from the lesion, use three or four doses and if more are necessary make up a new vaccine.
If the above statements are borne in mind and vaccines are made and administered accordingly, the author is well satisfied that much better results will be secured.
In accordance with the theory on which the use of vaccines is based, i.e., that they stimulate the body cells to produce immunizing antibodies, it is clear that they are especially suitable in those infections in which the process is localized and should not be of much value in general infections. In the latter case the cells of the body are stimulated to produce antibodies by the circulating organisms, probably nearly to their limit, hence the introduction of more of the same organisms, capable of stimulating though dead, is apt to overtax the cells and do more harm than good. It is not possible to tell accurately when this limit is reached, but the clinical symptoms are a guide. If vaccines are used at all in general infections they should be given in the early stages and in small doses at first with close watch as to the effect. In localized infections only the cells in the immediate neighborhood are much stimulated, hence the introduction of a vaccine calls to their aid cells in the body generally, and much more of the resulting antibodies are carried to the lesion in question. Manifestly surgical procedures such as incision, drainage, washing away of dead and necrotic tissue with normal saline solution, not necessarily antiseptics, will aid the antibodies in their action and are to be recommended where indicated.
In the practical application of any remedy the dosage is most important. Unfortunately there is no accurate method of determining this with a vaccine. Wright recommended determining the number of the organisms per cc. as before mentioned, and his method or some modification of it is still in general use. From what was said with regard to variation, both in organisms and in individuals, it can be seen that the number of organisms is at least only a very rough guide. This is further illustrated by the doses of micrococcus (staphylococcus) vaccines recommended by different writers, which vary from 50,000,000 to 2,000,000,000 per cc. The author is decidedly of the opinion that there is no way of determining the dosage of a vaccine in the treatment of any given case except by the result of the first dose. Hence it is his practice to make vaccines of a particular organism of the same approximate strength, and to give a dose of a measured portion of a cubic centimeter, judging the amount by what the individual or animal can apparently withstand, without too violent a reaction. If there is no local or general reaction or if it is very slight and there is no effect on the lesion, the dose is too small. If there is a violent local reaction with severe constitutional symptoms clinically, and the lesion appears worse, the dose is too large. There should be some local reaction and some general, but not enough to cause more than a slight disturbance, easy to judge in human subjects, more difficult in animals. In cases suitable for vaccine treatment no serious results should follow from a properly prepared vaccine, though the process of healing may be delayed temporarily. Wright claimed, and many have substantiated him, that always following a vaccination there is a period when the resistance of the animal is diminished. This is called the “negative phase,” and Wright considered this to last as long as the opsonic index remained low, and when this latter began to increase the stage of the “positive” or favorable phase was reached. As has been stated the opsonic index is pretty generally regarded as of doubtful value, though the existence of a period of lowered resistance is theoretically probable from the fact that antibodies already present in the blood will be partially used up in uniting with the vaccine introduced and that the body cells are called upon suddenly to do an extra amount of work and it takes them some time to adapt themselves. This time, the “negative phase,” is much better determined by the clinical symptoms, general and especially local. It is good practice to begin with a dose relatively small. The result of this is an indication of the proper dosage and also prepares the patient for a larger one. The second dose should follow the first not sooner than three or four days, and should be five to seven days if the first reaction is severe. These directions are not very definite, but clinical experience to date justifies them. It is worth the time and money to one who wishes to use vaccines to learn from one who has had experience both in making and administering them, and then to remember that each patient is an individual case, for the use of vaccines as well as for any other kind of treatment.
AGGRESSIN.
Opsonins have been shown to be specific substances which act on bacteria in such a way as to render them more readily taken up by the leukocytes. By analogy one might expect to find bacteria secreting specific substances which would tend to counteract the destructive action of the phagocytes and bactericidal substances. Bail and his co-workers claim to have demonstrated such substances in exudates in certain diseases and have given the distinctive name “aggressins” to them. By injecting an animal with “aggressins,” antiaggressins are produced which counteract their effects and thus enable the bacteria to be destroyed. The existence of such specific bodies is not generally accepted as proved. The prevailing idea is that bacteria protect themselves in any given case by the various toxic substances that they produce, and that “aggressins” as a special class of substances are not formed.