LIVE POLIO IRUS VACCINES

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Behavior of Cold Mutants of Poliovirus in Human Beings 107 tained with the "Glenn" strain of Type 3 virus. With the 250 C. variant of the "Glenn" strain it was possible to inoculate as many as one hundred million tissue-culture infective doses intraspinally without producing either paralysis or significant lesions. With the exception of a few perivascular infiltrations around the site of inoculation, there was usually no evidence of any histologic change that was different from that found in monkeys inoculated only with control, uninfected fluid. I should like to describe now what happened on tests in human beings. These tests were carried out at a foundling hospital in New York City in February. The interesting thing is that even though it was wintertime, and even though this was one of the most sanitary institutions I have ever been in, about 16 of the first group of 23 children had their own viruses in the stool before we started. Actually, most of them were very slow in growing; most of them were adenoviruses. To summarize, with the first Type 1 strain mentioned previously, i.e., P 2149, in a dose of 10". 5 TCD 5 , in five children, there was neither antibody formation nor multiplication even in the absence of any interfering agent. With the second strain, "P 2226", which multiplied a little faster at 360 C. in tissue culture we have two groups of children by now. In one group of 5, that received 10.- 6 TCD,, in 0.01 ml. antibody formation occurred in only two, one very late. With the larger dose of 107 'TCD, 5 0; only one out of four had multiplication and antibody formation. It is evident that both of these Type 1 strains lost their capacity for adequate multiplication in the human intestinal tract. The Type 2 strain was tested in a dose of 106'7 and 10 7 ,7TCDso in a total of eight children without homotypic antibody. It multiplied a little in one or two children, with development of a low antibody titer, and in the others it did not multiply at all. However, the Type 3 "Glenn" strain, although it was quite similar to the Type 1, P 2226 strain in its behavior in tissue culture, multiplied very well in the children despite the presence of interfering agents. This particular mutant multiplies extensively at 25 ° C. We obtained culture fluids 10 9 TCD,, per ml. On the first test with 0.01 ml., multiplication and antibody formation were found in only five out of seven children, but when we re-fed one of the negative children with the same dose, the virus multiplied and antibody developed. We performed another test with 0.01 ml. in three additional children and it multiplied in all, with antibody forming in all. With the larger dose of 0.1 ml., i.e., 10 8 TCD 5 0 , in six children, virus multiplication and antibody formation occurred in all. With 0.001 ml., i.e., 10 6 TCDo 0 we seem to have reached a probable 50 per cent end-point: it was three out of five. The level of virus multiplication was very often in the range of 500,000 to 1,000,000 tissueculture doses per gram of feces. Now comes the interesting thing of what happens to this virus after multiplication in the gastrointestinal tract. We have a very interesting marker here, the 250 C. marker, which is possessed by very few viruses. What we found, in brief, is that within a few days after multiplication in the intestinal tract, the capacity to multiply at 25 ° C. was not lost, but there appeared virus particles with the capacity to multiply at 400 C. The original stool may have only 1 per cent or less of the total virus that can multiply at 400 C. but after one passage in tissue culture at 36' C. one can obtain cultures that yield about the same titer at 400 C., 36 ° C., and 25 ° C. Thus, the cultures have not lost their capacity to grow well at 250 C., but have gained the capacity to grow at 40 ° C. This is remarkable because we have all found this with Type 3 viruses and it happens with all strains. The capacity for multiplication at 40 ° C. is something that is quickly acquired in a part of the population when it multiplies in the intestinal tract. As stated previously, it does not necessarily bear any relationship to neurovirulence as tested in monkeys. We have not yet had time to test the 250 C. excreted viruses in monkeys. To summarize, it is quite clear that the Type 1 and Type 2 25 ° C. viruses, which retained the capacity to multiply in tissue culture at 36 ° C. multiplied so poorly in the intestinal tract of human beings that they would be quite worthless as immunizing agents by the oral route. The Type 3 "Glenn" virus does seem to multiply well. It undergoes changes, at least as regards its reproductive capacity at 400 C., which are similar to those observed with the present Type
108 Safety-Laboratory Evidence of Attenuation and Safety 3 vaccine strains that have been studied. Future whether this Type 3 strain would have any tests will show whether or not the monkey neu- superior qualifications over the others, but I rovirulence tests on excreted virus will be very think it has thrown a great deal of light on the different from those that we obtained with the relationship between reproductive capacity in present strain. tissue cultures and reproductive capacity in the Accordingly, at the present time I do not know intestinal tract.
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LIVE POLIO IRUS VACCINES Papers Pre
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SECOND INTERNATIONAL CONFERENCE ON
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Preface The accumulation of informa
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Page 6. Vaccination of Full-Term In
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Page 23. Vaccination against Poliom
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Dr. Ghislain COURTOIS Director, Pri
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Dr. Edith PETTE Institute for the R
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4 Introductory Remarks 4 Introducto
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6 General Considerations immunity a
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8 General Considerations from accep
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10 General Considerations 10 Genera
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14 Safety-Laboratory Evidence of At
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- 26 Safety-Laboratory Evidence of
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DISCUSSION CHAIRMAN ANDERSON: There
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30 Discussion CHAIRMAN ANDERSON: Th
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32 TABLE 1. Safety-Laboratory Evide
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40 Discussion Of the 22 monkeys inf
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DISCUSSION CHAIRMAN ANDERSON: Thank
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46 Discussion a paralytic case. Thi
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48 Discussion + - + + I + - I + + 1
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50 Discussion sages of neurovirulen
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Application of Genetic Markers to D
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158 Discussion 158 Díscussion~~~~~
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160 Discussion specimens. We were u
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162 Safety-Field Evidence of Safety
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. . . 168 Safety-Field Evidence of
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14. THE CAPACITY OF LIVE ATTENUATED
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176 Saf ety-Field Evidence of Saf e
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Field, Laboratory Experiences With
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16. STUDIES ON LIVE POLIOVIRUS VACC
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Studies on Live Poliovirus Vaccine
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Da. HORSTMANN: If I may answer for
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Discussion 205 Discussion 205 tried
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NOTE: The Spanish translation of th
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Vaccination of Pregnant Women and Y
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Development and Persistence of Poli
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Virologic, Serologic Investigations
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_ _ _ _ _ _ _ _ Virologic, Serologi
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cARE NUC:4I Discussion 267 CUAw # J
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Discussion 269 in the investigation
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Virological Findings, Antibody Resp
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4. ROUTINE IMMUNIZATION WITH ATTENU
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Routine Immunization With Attenuate
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Experimental Infectionwith CHATAtte
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Experimental Infection with CHATAtt
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Experimental Infection with CHATAtt
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Vaccination of Full-Term Infants wi
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Response of Newborn Infants to Vacc
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Susceptibility of Newborn Infants t
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9. IMMUNIZATION OF NEWBORN INFANTS
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Immunization of Newborn Infants wit
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Discussion 323 vaccinated siblings
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Discussion 325 Discussion 325 ance
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transplacental antibodies, or antib
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Discussion 329 Discussion 329 born
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Recent Experience with Lederle Triv
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11. FURTHER EXPERIENCES WITH ORAL P
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Further Experiences with Oral Polio
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Minnesota Studies with Oral Poliomy
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13. USE OF ATTENUATED LIVE POLIOVIR
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Use of Attenuated Live Poliovirus V
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Use of Attenuated Live Poliovirus V
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DISCUSSION CHAIRMAN LÉPINE: The tw
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Discussion 373 -~~~~~~ics o 7 domin
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Discussion 375 -~ ~~~~isuso 7 DR. C
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i 14. EFFECTS OF RAPID MASS IMMUNIZ
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Live Poliovirus Immunization-Condit
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Use of Sabin's Live Poliovirus Vacc
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- Use of Sabin's Live Poliovirus Va
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TABLE 14. Use of Sabin's Live Polio
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Discussion 411 DR. ANDERSON: My que
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Course of Mass Immunization in USSR
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, _ _ Course of Mass Immunization i
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DISCUSSION CHAIRMAN LÉPINE: Thank
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Discussion 431 DR. STUART-HARRIS: I
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436 Efficacy-Field Evidence TABLE 1
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438 Efficacy-Field Evidence Adminis
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444 Effcaey-Field Evidence 44 Efiay
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446 Efficacy-Field Evidence 446 Eff
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448 Efficacy-Field Evidence 448 lEf
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450 Efficacy-Field Evidence m Co 0
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452 Efficacy-Field Evidence ] ~~ ~
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454 Efficacy-Field Evidence It is n
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456 Efficacy-Field Evidence M.G. C
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458 Discussion 458 Discussion~~~~~~
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462 Discussion one was sponsored by
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Vaccination with CHAT Strain Type 1
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Live Virus Vaccine Studies in South
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Discussion 481 the ages of the five
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Immunological and Epidemiological E
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Further Observations on First Field
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Further Observations Qn First Field
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Further Observations on First FielJ
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Poliomyelitis Vaccination in Poland
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Live Poliomyelitis Vaccine-Small-Sc
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25. VACCINATION AND CHALLENGE-POLIO
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Discussion 575 ence last year. The
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Large-Scale Practical Trials, Use o
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594 Discussion 594 Disenísion ~ ~
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596 Discussion 596 Díscussion~~~~~
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598 Discussion 598 Discussion high
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602 Summary of the Conference 602 S
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Appendix The following letter was r
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608 Index Antibodies-continued half
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610 Index Bulychev, N. P., paper, 4
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612 Index Coxsackie--continued B-3
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614 Index Epidemics-continued intro
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616 Index Genetic stability-continu
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618 Index Infants-continued source
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620 Index Laboratory surveillance d
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622 Index Monkey neurovirulence, 95
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624 Index pH neutralization test, 6
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626 Index Poliomyelitis virus-conti
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628 Index Serological response-cont
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630 Index T marker-continued T- str
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632 Index Vaccine, Attenuated-conti
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634 Index Virus isolations and anti
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