LIVE POLIO IRUS VACCINES

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Discussion 47 ble, by introduction into children, of producing viremia which is not usually observed with original strains. We therefore took monolayer cultures and conducted blood tests on children at various periods after the introduction of such strains to test the possible appearance of viremia and the increase of neurovirulence. The results are now in progress, but we have preliminary data with Type 3 strain which show that this more neurovirulent strain does not cause viremia in children. I believe that these results are more important for the evaluation of safety of these viruses than are the various laboratory markers, which are so interesting in theoretical investigations of different variants. Viremia, after all, is the first stage which can be a menace to the generalization of such viruses into the central nervous system and its evaluation, among other markers, seems to be an especially important task. DR. DULBECCO: The question of relationship between various markers and neurovirulence is actually a part of the general problem of correlation in variation of markers of any kind that occurs in poliovirus. In the work carried out in our laboratory by Dr. McBride, Dr. Vogt, and myself, we have obtained the information which is summarized in Table 1. We have markers which show extreme cystine requirement, the inhibition by cystine, the temperature resistance for inactivation, the d character, the 30 and 40 centigrade growth, the MS marker, the resistance to inhibitors, and neurovirulence. Now, there are many pluses and many minuses. The plus indicates, in a qualitative way, that the coexistence of the markers in the same virus is possible and frequent. The minus indicates that very frequently we have exclusion between these markers. Now there are exceptions as we very well know. You will note that there are quite a number of minuses, meaning that if mutation occurs, let us say, from the d plus to the d, then it is very likely that at the same time the temperature resistance marker will also change simultaneously. A close look at the minuses shown in Table 1 will reveal that these concern essentially a group of markers which include the temperature resistance, the 30 and 40 degree growth, the MS character, the d character, cystine requirement, and neurovirulence. The bovine and equine inhibitor markers are completely out of the group. This means that whenever a marker in this group changes, the bovine or equine inhibitor markers are not affected, and vice versa. Therefore, all the markers constitute two groups. In one there is an extensive degree of covariation, meaning that a variation of one marker may involve a variation of another one, or variation of one marker may cause exclusion of another marker. I believe that, in general, the use of markers serves a dual purpose in the study of vaccines. One of these would be, as emphasized very frequently at this session, to have markers that can be used as in vitro markers for neurovirulence. The other would be to have a marker which can be used to trace a certain strain introduced in the population, in order to determine, for instance, whether the strain recovered is identical to the strain which was introduced. Markers of the first group may be useful for the first purpose. For the second purpose, it is obvious that none of the markers in this group is useful because if a mutation arises, it may involve the marker employed. Only the bovine and equine markers are suitable for the second purpose. Perhaps the marker of antigenicity referred to earlier could be considered. As for the covariation of markers of the first group, many exceptions have already been pointed out. None of these markers truly reflects the behavior of neurovirulence. This also raises further questions: the direction that research will have to take in this field and the significance of all these findings. I should like to call attention to a theoretical point, namely, the fact that we have so many different markers for poliovirus does not imply that we have many genes in the poliovirus. The hypothesis of many genes, which may seem to be the simplest explanation, does not take into account two facts: one, the construction of the virus; the other, the extent of covariation. If there were different genes, one would not expect this extensive covariation. The structure of the virus is against the hypothesis of many genes because we know that the RNA of poliovirus, the genetic material, is very small, of a size equivalent to that considered as
48 Discussion + - + + I + - I + + 1 + + + + + I I I I + + + + + + + 1 + +++++~~~~~~~~~~~~~~~~~~~~~~~l + . + .. - lo + + + + + + + + + + + + + Q ++++++ +++ ++ Mr + + I + I + + + I o Mr 1 + + + + . EP. 4 o oÍ p3 z E- ,i o ¡ + + - + + - . + .- - . . . q ,+: . .. . _- _ r... .,-- + + I + I o Co 1 + + + + + F I b = x +1 u : + + 1 ,b E. , .q lo b -Q 0r 04 o- o K C. Q b V> u 00 b Qc: -+ I-- ¡ r:- ~~ .. .. ¡ql [+J - ¡ 1 +I¡ : U >; a a m s_ i 0 0 .0 0 0 ° zE 11 11 + I
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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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Laboratory Investigations of Attenu
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Discussion 99 In the case of Table
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8. BEHAVIOR OF COLD MUTANTS OF POLI
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Behavior of Cold Mutants of Poliovi
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DISCUSSION CHAIRMAN BURNET: Thank y
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114 Safety-Field Evidence of Safety
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118 S afety-Field Evidence of S af
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122 Discussion 122 Discussion~~~~~~
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10. LABORATORY INVESTIGATIONS OF TH
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126 VIRUS 1 MAhONEY Safety-Field Ev
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128 Safety-Field Evidence óf Safet
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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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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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Further Observations on 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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Discussion 575 ence last year. The
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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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