LIVE POLIO IRUS VACCINES

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Experimental Studies on Animals with Attenuated Poliovirus 77 depend on the extent and occurrence of central nervous system lesions, i.e., animals in which I.S. inoculation did not reach the grey substance of the lumbar cord, also showed antibody formation. Differences between the strains examined seem to occur only with regard to Type 3, of which Sabin's strain led to antibody production in only one case (see Table 5). The antibody titer was partly high and in some cases exceeded a dilution of 1:512. The various strains showed no difference in the height of titers. (e) Virus isolation from feces: 627 specimens of feces were examined before and during the experiment. In 206 cases a cytopathogenic effect could be found in tissue cultures (43 cases showed the type of cytopathogenic effect found with adenovirus, in 159 cases it had not yet been possible to determine the type, in 4 cases poliovirus was isolated). Discussion. Our findings with regard to the neuropathogenicity of the attenuated virus strains of Sabin and Cox are in agreement with the results of Murray and Melnick, i.e., all three of Sabin's intraspinally inoculated strains are less neuropathogenic than those of Cox. This difference was most striking in the Type 2 strains, whereas there was no difference following intracerebral inoculation of Type 1 strains of Sabin and Cox. A comparison with Murray's findings regarding the extent of neuropathogenicity showed that in our examinations Cox's Type 1 led to less pronounced histological lesions in the central nervous system. Results with Types 2 and 3 of Cox tallied quite well with the findings of Murray. With Sabin's Types 2 and 3 strains, the alterations found by us were similar to Murray's findings. This was also the case with Type 1 following I.C. inoculation. Following I.S. inoculation, the alterations found by us were less pronounced. A comparison of our findings with those of Cabasso using the Cox strains revealed a higher degree of neuropathogenicity following I.S. inoculation of Type 1. There was no difference in results following I.C. inoculation. With Type 2 we found histological alterations more frequently than Cabasso following I.S. as well as I.C. inoculation. A comparison of results with Type 3 was not possible. An attempt to isolate the virus from the central nervous system after the end of the observation period showed striking differences between the various strains. The rate of successful isolations essentially paralleled the neuropathogenicity found by histological examination. The examination of genetic properties of isolated strains using markers d, T, and MS occasionally showed slight alterations of some characteristics in comparison to the initial material. Cox's Type 2 seems to possess the greatest stability with respect to the examined genetic markers. There was no difference in the production of antibodies following I.C. and I.S. inoculation; particularly, there was no relationship with the occurrence and extent of histological lesions in the central nervous system. Noteworthy was the fact that antibody production was rare following inoculation of Sabin's Type 3 strain. No connection was found between antibody production and the frequency of isolation of non-poliovirus from the feces of the animals. The antibody formation is regarded as proof of a multiplication of virus outside of the central nervous system, with the spreading of the virus obviously taking place directly via the inoculation trauma. The validity of this statement was supported by the results of experiments on the inoculation of india ink into the central nervous system. Finally we would like to raise the question of whether, in addition to the usual methods of testing the neuropathogenicity of virus, other criteria might also be useful in assessing the suitability of strains for human vaccination. Of these, one might name the obvious multiplication of virus in the central nervous system, the ability to multiply outside of the central nervous system and the genetic stability of virus strain following passage in neural and extraneural tissue. CONCLUSION By intracerebral and intraspinal inoculation of monkeys with the attenuated poliovirus strains of Sabin and Cox it was shown that all three of Sabin's strains are less neuropathogenic than those of Cox. These results are in agreement with the findings of Murray and Melnick. At the end of the observation period of 21 days, the results of virus isolations from the central nervous system paralleled those on neuropathogenicity as manifested by histological alter-
78 Safety-Laboratory Evidence of Attenuation and Safety ations. In tests with genetic markers d, T, and MS the strains isolated revealed only occasional and slight alterations in comparison to the initial material. While following passage through the central nervous system they did not present in one single instance the characteristics of virulent strains. In tests on antibody formation following intraspinal and intracerebral inoculation, antibodies were seldom produced following the use of Sabin's Type 3 strain. The possibilities for determining neuropathogenicity and the question of further criteria for the evaluation of these vaccines are discussed.
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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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128 Safety-Field Evidence óf Safet
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130 Safety-Field Evidence of Safety
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DISCUSSION CHAIRMAN ZHDANOV: This p
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11. EPIDEMIOLOGICAL AND VIROLOGICAL
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12. SPREAD OF A VACCINE STRAIN OF P
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148 Saf ety-Field Evidence of Saf e
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152 Saf ety-Field Evidence of Safet
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DISCUSSION CHAIRMAN ZHDANOV: The pa
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158 Discussion 158 Díscussion~~~~~
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160 Discussion specimens. We were u
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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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460 460 Discussion 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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DISCUSSION CHAIRMAN STUART-HARRIS:
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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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24. A SMALL-SCALE TRIAL WITH LIVE P
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Live Poliomyelitis Vaccine-Small-Sc
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25. VACCINATION AND CHALLENGE-POLIO
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Vaccination and Challenge-Poliomyel
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26. VACCINATION WITH ATTENUATED POL
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Vaccination with Attenuated Poliovi
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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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LIVE POLIO IRUS VACCINES

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