LIVE POLIO IRUS VACCINES

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Laboratory Investigations of Attenuated Vaccine Strains 125 sons fed trivalent Lederle vaccine were incubated for 1 hour at 37 ° C. with divalent rabbit, antipoliovirus serum (50 MIT units of each antibody per 0.1 ml.) so that single poliovirus types could be studied. Viral titrations were performed in Rhesus kidney-cell culture tubes containing Earle's balanced salt solution (0.22 per cent sodium bicarbonate) and 0.5 per cent lactalbumin hydrolysate. Plaque assays were done in 2 oz. bottles using the same medium containing 20 per cent skim milk. 4 Temperature (T) characteristics were determined by incubating half the inoculated culture tubes or plaque bottles in a 36.0° - 0.3 incubator and half at an incubator temperature of 39.5 ° C. or 40.0 ° C. A final reading was done on the sixth or seventh day. Tests included the appropriate controls with seed virus strain as well as the virulent Mahoney Type 1 strain. T character is expressed as log,, titer at 360 C. minus log,, titer at 39.5 ° C. or 40 ° C. Plaque diameter T character is a ratio of the diameter at 39.5 ° C. over diameter at 36 ° C. expressed as per cent. Neurovirulence of virus preparations for monkeys was determined by inoculating amounts of virus calculated to be at the end-point of infectivity for the homotypic seed virus. Three Rhesus monkeys were inoculated by each route, intrathalamically (I TH), intraspinally (IS), and intramuscularly (IM)-a total of nine monkeysobserved for paralysis, sacrificed 14 to 21 days after inoculation and portions of the CNS were examined histopathologically by methods previously described. 2 ' 3 Monkey neurovirulence results are expressed as the maximum plaqueforming units (PFU) of virus causing no lesions (threshold) . RESULTS Comparison of T Character and Monkey Neurovirulence. The T character may be measured by several methods, including monkey-kidney cell culture tube titration, plaque count assay and the measurement of plaque diameter as determined at 36 ° C. and 39.5 ° C. To determine which of these techniques best correlates with neurovirulence for monkeys, a comparison was made with the results of monkey studies previously reported from this laboratory. 2 ' In the results presented in Fig. 1 each T characteristic is the average of three separate determinations. A shorter line for T character indicates increased ability to grow at 39.5 ° C. and a shorter line for monkey neurovirulence indicates increased virulence. No determination is indicated by absence of a line. The plaque count determination of T character of Types 1 and 2 appears to be correlated better with monkey neurovirulence following CNS inoculation than do the tube titration or plaque diameter methods. This correlation is especially striking with the Lederle Type 2 strain which shows higher neurovirulence following CNS inoculation; however, this strain shows a tube titration T characteristic suggestive of low virulence, whereas the plaque count T character indicates greater virulence. There was poor correlation between all T determinations and monkey virulence in the case of each Type 3 strain. In addition, correlation is lacking between the T characteristic and neurovirulence following IM inoculation. The latter observations are consistent with other data indicating that neurovirulence following IM inoculation appears to measure different properties than does direct central nervous system (CNS) inoculation. 5 ' During the course of this study it was noted (Fig. 2) that there was a considerable differential of virus growth when temperature of incubation was raised from 39.5 ° C. to 40 ° C. - 0.3. While the indicated temperature difference was 0.5 ° C., we could not exclude a somewhat greater difference due to a temperature variation of -0.3 ° C. within the incubators and due to a variation of --0.2 ° C. between thermometers. The higher temperature permitted better differentiation of virus strains but the overall ranking of virulence by T character remained the same. In addition the ranking by T character of the Type 3 strains appeared better correlated with neurovirulence for monkeys following CNS inoculation when the higher temperature of incubation was 40 ° C. rather than 39.5 ° C. As a result of these experiments, plaque count assay was adopted as a reasonable screening test for the detection of changes in neurovirulence of monkeys inoculated I TH or IS. Effect of Laboratory Manipulation on the T Character and Monkey Neurovirulence. Alteration of the T character and monkey neurovirulence has been reported to be associated with laboratory manipulation of attenuated viruses.?
126 V<strong>IRUS</strong> 1 MAhONEY Safety-Field Evidence of Safety END.POINT 36 C. MINUS END-POINT 39.5 C. TCID 5 0 PFU PLAQUE DIAM I TH IS I MAXIMUM PFU CAUSING NO LESIONS IM K L - '5 S 2 MEFI K L -5) S 3 SALK 0011 K r l l J , i L 4 1 1 1 1 1 . . . O 1 2 3 4 5 0 1 2 3 4 5 6 O 40o 800 LOO i 2 3 4 5 6 i1 2 3 4 5 6 O 2 3 4 5 6 7 8 ° ' _ LoglO 0 I L°° 10 1 0 lo I LoglO Lolo0 FIc. 1. T character and monkey neurovirulence. Virus PFU 360 C./39.5 0 C. PFU 36 ° C./40 0 C. Log 10 Log 10 Source K1 L1 L2 L3 S3 MAHONEY 0 1 2 3 4 5 6 0 1 2 3 4 5 6 7 FIG. 2. T character 36°C./39.5°C. and 40.0°C.
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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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Discussion 67 TABLE 1. INCIDENCE OF
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Experimental Studies on Animals wit
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176 Saf ety-Field Evidence of Saf e
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180 Safety-Field Evidence of Safety
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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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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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Vaccination with Attenuated Poliovi
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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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LIVE POLIO IRUS VACCINES

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