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LIVE POLIO IRUS VACCINES

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7. LABORATORY INVESTIGATIONS OF THRE ATTENUATED<br />

<strong>POLIO</strong>V<strong>IRUS</strong> VACCINE STRAINS<br />

I. NEUROVIRULENCE AFTER INTRAMUSCULAR INOCULATION OF<br />

MONKEYS<br />

R. KIRSCHSTEIN, G. BORMAN, S. BARON, R. FRIEDMAN, R. MURRAY, AND G. HOTTLE<br />

Division of Biologics Standards<br />

National Institutes of Health, Bethesda, Maryland<br />

DR. KIRSCHSTEIN (presenting the paper): At<br />

the First International Conference on Live Poliovirus<br />

Vaccines last year we presented a comparison<br />

of the neurovirulence of the attenuated poliovirus<br />

vaccine strains when inoculated directly<br />

into the central nervous system (CNS) of monkeys<br />

1. As you heard this afternoon, Dr. Pette<br />

confirmed our observations.<br />

The significance of those results and the correlation<br />

of neurovirulence after that type of inoculation<br />

with neurovirulence in man is not<br />

really known. Therefore, it appeared that a<br />

study of the neurovirulence of the attenuated<br />

strains after inoculation extraneurally might be<br />

more meaningful and add to our knowledge of<br />

the invasiveness of these strains.<br />

Preliminary studies of these strains after intramuscular<br />

inoculation have been performed<br />

before by Sabin in 1957 2 and by ourselves and<br />

Melnick in our laboratory 3 in 1958.<br />

Monkeys: The majority of monkeys used in<br />

this study were Rhesus (Macaca mulatta). A<br />

small number of Cynomolgus (Macaca irus phillipinensis)<br />

monkeys were also used. The animals<br />

were in overt good health and weighed<br />

between 4-10 lbs. initially. The animals were<br />

observed daily for signs of poliomyelitis and<br />

were sacrificed at 14-20 days. They were housed<br />

in stainless steel double-decked cages with 2 or<br />

3 per cage.<br />

Virus strains: The virus strains were obtained<br />

from Dr. Koprowski, from Lederle Laboratories<br />

and from Dr. Sabin. The titers and identification<br />

of the virus strains are seen in Table 1.<br />

The virus fluids were titered as described in<br />

our paper at the first Conference. On the whole<br />

the titers were somewhat higher than those we<br />

obtained last year.<br />

Inoculation: The monkeys were inoculated<br />

into the right thigh, or upper arm muscles with<br />

1 ml., 5 ml., or 10 ml. amounts of undiluted<br />

virus fluids or 1 ml. amounts of material diluted<br />

1:10.<br />

Examination o! Tissues: The methods followed<br />

were those used in the safety test for inactivated<br />

poliomyelitis vaccine and were de-<br />

TABLE 1.<br />

STRAINS OF <strong>POLIO</strong>V<strong>IRUS</strong> STUDIED<br />

Koprowski group<br />

Type 1<br />

Type 2<br />

Type 3<br />

Lederle group<br />

Type 1<br />

Type 2<br />

Type 3<br />

Sabin group<br />

Type 1<br />

Type 2<br />

Type 3<br />

Wistar-CHAT Pool 13<br />

TN 19 Pool 1<br />

WFX Pool WY 13<br />

Lederle-SM, y 7-1231-166<br />

Lederle-MEF-1, M& 7-1232-243<br />

Lederle-Fox, M 7-1233-344<br />

L Se, 2 ab<br />

P 72, Ch, 2 ab<br />

Leon, 12 a, b<br />

107.2 PFU/ml.<br />

106'o PFU/ml.<br />

10' M 1 PFU/ml.<br />

107.9 PFU/ml.<br />

106 ' 5 PFU/ml.<br />

107.0 PFU/ml.<br />

107'7 PFU/ml.<br />

107 T 3 PFU/ml.<br />

1079 PFU/ml.<br />

90

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