Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/1998
Publication Date: N/A
Interpretive Summary: Following human vaccination against the virus causing polio, there is a rare incidence of one person per million vaccinated developing extensive paralysis. This paralysis is due to the live, safe vaccine virus reverting to a dangerous form. Because of this problem, the World Health Organization has requested that a new vaccine against polio be developed. Using an animal model of polio, we have developed a new, safer vaccine for polio. Furthermore, this new virus does not revert and thus does not cause paralysis. These results are important because they form the basis for the production of a new, safer vaccine for polio.
Technical Abstract: We have investigated the neurovirulence of a chimeric poliovirus consisting of the coding region of Lansing type 2 poliovirus and the 5# non-coding region (NCR) of type 3 poliovirus. Specifically, we carried out studies on the effects of stable base pairing, between nucleotides 472 and 537, on neurovirulence. Mice were injected intracranially with the attenuated chimeric virus MAS 27 plaque 1 having the following nucleotide base pair at 472-537, G-G. Mutants recovered from the central nervous system of inoculated mice were divided into 3 groups according to the nucleotide sequence of the 5# NCR; MAS 27C type viruses having a single base change (G-C) at position 472, MAS 27G type mutants having a single base change (G-C) at position 537, and MAS 27U type viruses having a single base change (G-U) at position 537. The isolate MAS 27C had back- mutated to the wild type, and was 100,000-fold more virulent than attenuated MAS 27G and MAS 27U. MAS 27C type mutants were predominant, suggesting that base C at position 472 is favored to form a stable secondary structure with guanine at position 537. Attenuated MAS 27G, however, carries guanine and cytosine at nucleotides 472 and 537, respectively, and was a stable attenuated virus following passage in four serial generations of mice. Furthermore, attenuated MAS 27G poliovirus produced viral proteins less efficiently, and had slower growth rates than the revertant MAS 27C. The stable attenuated base paired MAS 27G might provide the basis for a prototype for a live attenuated stable type 3 poliovaccine.