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Persistence and class-specificity of neutralizing antibody response induced by trypsin-cleaved type 3 poliovirus in
M Roivainen1, L Piirainen, T Hovi
1Enterovirus Laboratory, National Public Health Institute, Helsinki, Finland.
Abstract:
Antibody responses in Balb/c mice immunized with different preparations of type 3 poliovirus/Saukett were compared. Live and formalin-inactivated virus preparations, either as such or after selective cleavage by trypsin, were used. The latter treatment is known to yield surface-modified virus particles similar to those generated during natural infection in man. We have previously shown that these modified viruses are poorly neutralized by sera from persons immunized solely with inactivated poliovirus vaccine. Trypsin-cleaved virus-immunized mice produced antibodies capable of neutralizing both virus preparations. Surprisingly, a major part of these neutralizing antibodies 5 months after the third dose were still of the IgM class. In contrast, antibodies from mice immunized with untreated, intact virus were mainly of the IgG class and they readily neutralized the immunogen itself but were not usually able to neutralize the trypsin-cleaved virus. These results indicate that neutralizing antibodies induced in Balb/c mice by trypsin-modified type 3 poliovirus show an 'improved' distribution of antigenic site specificities resembling that seen in man after poliovirus infection.
Insights
Mice immunized with modified poliovirus developed antibodies that neutralized both intact and modified virus. These antibodies, surprisingly, remained largely IgM, suggesting a distinct immune response to altered virus antigens.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- Poliovirus vaccines induce antibody responses that vary in their ability to neutralize different virus forms.
- Surface-modified poliovirus particles mimic those generated during natural infection.
- Previous studies indicated that inactivated poliovirus vaccine sera poorly neutralize modified poliovirus.
Purpose of the Study:
- To compare antibody responses in mice immunized with different preparations of type 3 poliovirus.
- To investigate the neutralizing capacity and antibody class of responses to intact versus trypsin-cleaved poliovirus.
- To assess if modified poliovirus immunization elicits antibody specificities similar to natural poliovirus infection.
Main Methods:
- Balb/c mice were immunized with live and formalin-inactivated type 3 poliovirus/Saukett preparations.
- Virus preparations were either intact or selectively cleaved by trypsin to create surface-modified particles.
- Antibody neutralization assays and immunoglobulin class determination (IgM/IgG) were performed at 5 months post-third dose.
Main Results:
- Mice immunized with trypsin-cleaved virus produced antibodies that neutralized both intact and cleaved virus preparations.
- A significant portion of neutralizing antibodies in mice immunized with cleaved virus remained IgM class 5 months after immunization.
- Antibodies from mice immunized with intact virus were primarily IgG, neutralized intact virus, but poorly neutralized cleaved virus.
Conclusions:
- Immunization with trypsin-modified type 3 poliovirus in mice induces neutralizing antibodies with broader antigenic site specificities.
- The antibody response to modified poliovirus, characterized by persistent IgM and broad neutralization, resembles that observed in human poliovirus infection.
- These findings suggest that surface-modified poliovirus may elicit a more comprehensive immune response compared to intact or inactivated virus preparations.