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LIVE POLIO IRUS VACCINES

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Discussion<br />

99<br />

In the case of Table 2, instead of gamma globulin<br />

we injected intramuscularly into the gluteus<br />

a commercial preparation of Tri-immunol, a vaccine<br />

containing pertussis, diphtheria and tetanus<br />

toxoids, and 8.6 logs of the Type 1 virus<br />

intravenously. Neither paralysis nor lesions occurred.<br />

In another experiment, Type 1 was injected<br />

intravenously and saline intracerebrally: the<br />

lesions were few and paralysis did not occur.<br />

One batch of Type 3 shown in the table gave essentially<br />

the same results.<br />

Perhaps the major point to be made is, as<br />

Dr. Kirschstein has already said, that this is<br />

not a case of a virus growing and spreading by<br />

the blood, since a vast dose intravenously and<br />

trauma intracerebrally or intramuscularly did<br />

not cause any paralysis.<br />

DR. MELNICK: Dr. Kirschstein mentioned the<br />

higher titers of virus found in 1960. I would<br />

like to know whether this represents new material,<br />

or 1959 material which was retitrated?<br />

DR. KIRSCHSTEIN:<br />

DR. MELNICK:<br />

1960?<br />

New material.<br />

Prepared between 1959 and<br />

DR. KIRSCHSTEIN: The material that Drs. Cox<br />

and Koprowski sent us were new lots from the<br />

same seed pools.<br />

DR. MELNICK: Could we have it for the record<br />

from those who submitted the new vaccines?<br />

DR. Cox: I would like to point out that<br />

some years ago we did inoculate monkeys in<br />

the deltoid and also with 5 cc. and 10 cc.'s intravenously,<br />

and we found nothing. I think<br />

that this discovery of the behavior of Type 1,<br />

by the intramuscular route in the buttocks, was<br />

made somewhat by accident. We had never<br />

inoculated monkeys by this route. Actually we<br />

did not know about this until last December<br />

after we had fed nearly one million people.<br />

We did not know that our Type 1 had this<br />

property.<br />

Of course, the question was then asked: What<br />

do you do in a case like this? Which are the<br />

more significant, 20 monkeys or one million<br />

people? Naturally we had to make a decision.<br />

Since the intramuscular activity was found we<br />

have confirmed it. We still have not been able<br />

to produce clinical reactions in monkeys by<br />

the intravenous route as Dr. Moyer has shown<br />

you, even when we inoculated monkeys intravenously<br />

with 10 cc.'s, and then tried to break<br />

their resistance by intracerebral injections with<br />

saline or other agents.<br />

This is a peculiar propertv. It has been<br />

found to exist at present in all Type 1 strains,<br />

to a greater extent in some than in others.<br />

You should keep in mind that we are not injecting<br />

man intramuscularly, but are feeding<br />

man orally. You should also keep in mind that<br />

these vaccines are intended to be used in a certain<br />

dosage and by a certain route. I should<br />

like to remind you that you never vaccinate<br />

people on the eyeball with smallpox. We know<br />

that they would be blinded under those conditions.<br />

Like everything else, further studies reveal<br />

new or unknown properties. This is not limited<br />

to polio research. This has been found<br />

with every virus that we have ever worked with.<br />

DR. KOPROWSKI: I would like to make a<br />

statement concerning gamma globulin. I strongly<br />

suspect that two factors are involved: One is<br />

the very high concentration of virus used and<br />

the other is the titer of antibodies in gamma<br />

globulin. Perhaps before Dr. Kirschstein can<br />

make a definite statement that gamma globulin<br />

administration has no protective effect, a titration<br />

of the virus in monkeys injected with high<br />

concentration of gamma globulin should be undertaken<br />

and compared with the results in controls.<br />

Now a short comment on viremia. 1 believe<br />

the problem of spillover versus multiplication<br />

can be settled if titration of the virus in blood<br />

can be performed at frequent intervals. If the<br />

concentration of circulating virus should drop<br />

in 24 hours or 48 hours after infection and later<br />

on rise again, we should consider that the virus<br />

multiplied in an organ communicating directly<br />

with the blood.<br />

Da. KIRSCHSTEIN: The dosage of gamma globulin<br />

given to these monkeys is that which Dr.<br />

Nathanson had used to prevent monkeys from<br />

becoming paralyzed and developing lesions, using<br />

Mahoney virus present in some partially inactivated<br />

poliovirus vaccine. It had been effective

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