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LIVE POLIO IRUS VACCINES

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328<br />

Discussion<br />

if we give the Blacksburg Newcastle vaccine<br />

(4.5 logs or better), either intranasally or in the<br />

eye, we find that they are rendered immune. I<br />

think this observation is an extremely important<br />

one and of value in polio work.<br />

Actually, the work which was done on Newcastle<br />

disease back in 1944 and 1945 by my colleague,<br />

Dr. Floyd S. Markham, highly influenced<br />

us to go in the direction of living virus vaccine<br />

in connection with the polio problem.<br />

DR. LÉPINE: I should like to confirm what Dr.<br />

Perkins said regarding the response of infants to<br />

antigenic stimuli, especially in the case of inactivated<br />

vaccine.<br />

A paper published recently by Dr. R. Grumbach<br />

et al., containing a study made with my<br />

laboratory's participation and presented at the<br />

October meeting of the C.I.E. in Paris, shows the<br />

response of infants immunized with inactivated<br />

polio vaccine combined with other antigens,<br />

namely, diphtheria, tetanus, and pertussis on<br />

two groups of children. In one group, there were<br />

infants from two to six months of age; in the<br />

second, children over six.<br />

After immunization, the response in infants,<br />

as judged by the antibody titers obtained, seemed<br />

to lag behind that in the older ones, and it therefore<br />

seemed at first that the results were not good.<br />

However, one year later, when they were given<br />

their booster dose, the infants' response jumped<br />

to exactly the same antibody level as that of the<br />

older children. So, even if the primary response<br />

in infants is not immediately so good as in the<br />

older children, they nevertheless keep the memory<br />

of the antigen and are later able to do as well<br />

as the older children.<br />

DR. KRUGMAN: I believe that the comments by<br />

Dr. Lépine and Dr. Perkins tend to confirm our<br />

impression that placentally transmitted antibody<br />

masks evidence of active antibody formation. I<br />

am reminded of a study which was carried out<br />

in our department in 1952 by Doctors Osborn and<br />

Dancis. Their studies were concerned with the<br />

effect of passive transplacental antibody on the<br />

active immunization of newborn infants with<br />

diphtheria toxoid. An injection of toxoid was<br />

followed by a rising titer of diphtheria antitoxin<br />

in infants with low levels of passive antibody and<br />

a declining titer in those with high levels.<br />

At six months, infants with the high level of<br />

transplacental passive antibody and lack of evidence<br />

of response were given another inoculation<br />

of diphtheria toxoid, which promptly induced a<br />

"booster" response. Accordingly, it appeared as<br />

if the initial high levels of passive antibody had<br />

"masked" the presence of active antibody. This<br />

phenomenon may explain the low percentage of<br />

antibody response in our high titer group.<br />

DR. DULBECCO: I should like to ask a question<br />

of a more general nature, namely, what is the<br />

feeling about the possible complication caused<br />

by simian virus, some of which are known and<br />

some possibly unknown, in the feeding of newborn<br />

children?<br />

In fact, the experimental work with animals<br />

has shown that at this age animals are particularly<br />

susceptible to carcinogenic viruses, of which<br />

some are active also in oral infections.<br />

CHAIRMAN HILLEBOE: Does anyone wish to<br />

comment on this?<br />

DR. KOPROWSKI: I should like first to comment<br />

about immunologic tolerance. Although I recognize<br />

this phenomenon as an important biological<br />

problem, we have no evidence that it plays any<br />

role in virus infection, except possibly the<br />

lymphocytic choriomeningitis infection of mice.<br />

Even in that case, the available evidence is still<br />

not completely satisfactory because the crucial<br />

experiments have not been performed.<br />

I must say that we have completed a two-year<br />

study of attempts to induce tolerance in mice to<br />

the three viruses: rabies and two Arbor B viruses.<br />

If these observations are ever written up, they<br />

will be submitted to the "Journal of Negative<br />

Results."<br />

If we want to study tolerance in virus diseases,<br />

our efforts should be directed to infections which<br />

do not induce formation of demonstrable antibodies,<br />

such as African swine fever, equine infectious<br />

anemia, or serum hepatitis. Our efforts<br />

are largely wasted in the case of diseases like<br />

poliomyelitis, where antigenic stimulus almost<br />

invariably causes antibody formation.<br />

In one case of possible fetal infection of man,<br />

that of German measles virus, tolerance does not<br />

play any role. 1 have asked Sir Macfarlane Burnet<br />

on several occasions about children who were

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