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LIVE POLIO IRUS VACCINES

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Application of Genetic Markers to Development and Control of Vaccine 61<br />

its first human passage strains. These preliminary<br />

data seem to indicate that the cold variant<br />

of the W1-P strain retains its infectivity for the<br />

human intestinal tract, as do other attenuated<br />

Type 1 strains, and does not undergo marked<br />

changes in its growth characteristics under different<br />

temperatures after one passage through the<br />

human intestinal tract. It must be emphasized<br />

that these are very preliminary results, obtained<br />

on a small number of individuals and subject to<br />

possible revision when more extensive data are<br />

obtained. Similar data are now being sought for<br />

the Type 3 virus, where development of a new<br />

and improved attenuated strain is much more<br />

imperative than in the case of the two other<br />

types of poliovirus.<br />

Inquiry into the Nature of MS and Temperatare<br />

Markers. Although genetic markers for<br />

poliovirus and other viruses have been employed<br />

in laboratory investigations for some time, the<br />

nature of these markers seems to be somewhat<br />

illusive. As shown in Table 13, the MS cell<br />

monolayer infected with CHAT virus will yield<br />

much smaller quantities of virus than parallel<br />

infection of fresh monkey-kidney culture. However,<br />

if, instead of intact virus, infectious nucleic<br />

acid isolated from the CHAT strain is used as the<br />

inoculum, the yield from MS cells will be greater<br />

than from monkey-kidney cells and similar to<br />

that obtained with either intact virus of the<br />

virulent Mahoney strain or infectious nucleic<br />

acid isolated from this strain. These results<br />

seem to indicate that in the process of attenuation<br />

the protein coat loses some of its ability to attach<br />

itself to the receptors and penetrate the<br />

cells of the established monkey-kidney line. In<br />

contrast, the nucleic acid part of the attenuated<br />

strains, which does not seem to need receptors to<br />

penetrate the cells, infects the MS cells at the<br />

same rate as a virulent intact virus. Thus results<br />

obtained with the CHAT strain and the MS cells<br />

are somewhat similar to those of Holland et al. 6<br />

for cell systems which are resistant to poliovirus.<br />

Obviously, the parallel cannot be drawn too<br />

closely, since ultimately the attenuated poliovirus<br />

can be propagated in the MS line, in contrast to<br />

Log. 10<br />

PFU /ml.<br />

-8-<br />

-6<br />

-1637-<br />

-400 C.<br />

°<br />

C.<br />

/<br />

/<br />

/<br />

/ /<br />

-MA4H<br />

B210<br />

/<br />

B207 .--- e<br />

- - _- _ --- B2 -4<br />

-4-<br />

- -c<br />

-YjW_, - -<br />

------- -<br />

l<br />

2<br />

I·<br />

- i - I<br />

I I<br />

6 10 Hrs.<br />

i<br />

FIG. 1

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