Abstract
Previous studies showed that the distribution of antigenic site specificity of neutralizing antibodies to type 3 poliovirus obtained with the inactivated poliovirus vaccine can be deficient as compared with that obtained following poliovirus infection. This observation was shown by the relatively low capacity of sera from inactivated-poliovirus-vaccine-immunized persons to neutralize poliovirus cleaved at antigenic site 1. We investigated possibilities for improving the situation in a mouse model. Balb/c mice were immunized with intact or trypsin-cleaved type 3 poliovirus (Saukett strain). Sera from mice immunized with the intact virus readily neutralized the intact virus but neutralized the cleaved virus only rarely. In contrast, cleaved-virus-immunized mice produced antibodies that were able to neutralize the cleaved virus as well as the intact one. Mice immunized with a 100-fold-higher dose of the intact virus produced significant levels of antibodies to the cleaved virus, too. Somewhat surprisingly, mice immunized with high doses of the cleaved virus produced antibodies specific for the intact loop between beta sheets B and C of VP1 (virion protein 1), which should be cleaved in the immunogen. This was shown by a higher titer of antibodies to intact Saukett virus than to the corresponding cleaved virus, as well as to a type 1/type 3 hybrid poliovirus in which only the BC loop amino acids were derived from type 3 poliovirus. The cleavage-induced enhanced availability of antigenic determinants residing outside the BC loop was also shown by increased neutralization titers of monoclonal antibodies specific for some of these other determinants. These results indicate that by using a trypsin-cleaved type 3 poliovirus as a parenteral immunogen, it is possible to change the distribution of antigenic site specificities of neutralizing antibodies to resemble that following poliovirus infection.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Fricks C. E., Icenogle J. P., Hogle J. M. Trypsin sensitivity of the Sabin strain of type 1 poliovirus: cleavage sites in virions and related particles. J Virol. 1985 Jun;54(3):856–859. doi: 10.1128/jvi.54.3.856-859.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hovi T., Roivainen M. Radiometric cytolysis inhibition assay, a new rapid test for neutralizing antibodies to intact and trypsin-cleaved poliovirus. J Clin Microbiol. 1989 Apr;27(4):709–715. doi: 10.1128/jcm.27.4.709-715.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Icenogle J. P., Minor P. D., Ferguson M., Hogle J. M. Modulation of humoral response to a 12-amino-acid site on the poliovirus virion. J Virol. 1986 Oct;60(1):297–301. doi: 10.1128/jvi.60.1.297-301.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kinnunen L., Hovi T. Partial RNA sequencing of eight supposed derivatives of type 3 poliovirus/USA/Saukett/50 reveals remarkable differences between three apparent substrains. Virology. 1989 May;170(1):316–320. doi: 10.1016/0042-6822(89)90387-5. [DOI] [PubMed] [Google Scholar]
- Minor P. D., Ferguson M., Evans D. M., Almond J. W., Icenogle J. P. Antigenic structure of polioviruses of serotypes 1, 2 and 3. J Gen Virol. 1986 Jul;67(Pt 7):1283–1291. doi: 10.1099/0022-1317-67-7-1283. [DOI] [PubMed] [Google Scholar]
- Murray M. G., Kuhn R. J., Arita M., Kawamura N., Nomoto A., Wimmer E. Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys. Proc Natl Acad Sci U S A. 1988 May;85(9):3203–3207. doi: 10.1073/pnas.85.9.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roivainen M., Hovi T. Cleavage of VP1 and modification of antigenic site 1 of type 2 polioviruses by intestinal trypsin. J Virol. 1988 Sep;62(9):3536–3539. doi: 10.1128/jvi.62.9.3536-3539.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roivainen M., Hovi T. Intestinal trypsin can significantly modify antigenic properties of polioviruses: implications for the use of inactivated poliovirus vaccine. J Virol. 1987 Dec;61(12):3749–3753. doi: 10.1128/jvi.61.12.3749-3753.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ukkonen P., Huovilainen A., Hovi T. Detection of poliovirus antigen by enzyme immunoassay. J Clin Microbiol. 1986 Dec;24(6):954–958. doi: 10.1128/jcm.24.6.954-958.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]