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Inactivated poliovirus vaccine protects transgenic poliovirus receptor mice against type 3 poliovirus challenge
R E Taffs1, Y V Chernokhvostova, E M Dragunsky
1Food and Drug Administration, Rockville, Maryland, USA.
Abstract:
Transgenic (Tg) mice expressing the human poliovirus receptor (PVR) were vaccinated with inactivated poliovirus vaccine (IPV) and evaluated for induced immunity against type 3 poliomyelitis. One injection of monovalent type 3 IPV elicited protective immunity against wild-type poliovirus. In contrast, 2 injections of trivalent IPV were required for protection. Neutralizing antibody response and protection were vaccine dose-dependent. Administration of polio-immune mouse plasma protected unimmunized mice, demonstrating that neutralizing antibody was sufficient for immunity. IPV heated to remove its D antigen component did not induce protection in Tg PVR mice. IPV derived from a wild-type poliovirus strain gave better protection against wild-type viral challenge than IPV derived from an attenuated poliovirus strain. The newly developed Tg PVR mouse-protection test may be useful in evaluating existing IPV potency tests and for attempts to improve formulations of trivalent IPV or combined vaccines for childhood immunization schedules.
Insights
Inactivated poliovirus vaccine (IPV) in transgenic mice showed that one dose of monovalent IPV protected against poliovirus, while trivalent IPV required two doses. Neutralizing antibodies were key for immunity.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Poliomyelitis remains a global health concern, necessitating effective inactivated poliovirus vaccine (IPV) strategies.
- Transgenic (Tg) mouse models expressing the human poliovirus receptor (PVR) offer a platform for studying poliovirus immunity.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of inactivated poliovirus vaccine (IPV) in a novel transgenic (Tg) mouse model expressing the human poliovirus receptor (PVR).
- To assess the role of neutralizing antibodies in protection against poliovirus infection using this model.
Main Methods:
- Transgenic (Tg) PVR mice were vaccinated with varying doses and formulations of inactivated poliovirus vaccine (IPV) (monovalent and trivalent).
- Mice were challenged with wild-type poliovirus, and protective immunity was assessed.
- Neutralizing antibody titers were measured.
- Passive transfer of immune plasma was performed to confirm antibody-mediated protection.
Main Results:
- A single dose of monovalent type 3 IPV conferred protection against wild-type poliovirus challenge in Tg PVR mice.
- Two doses of trivalent IPV were necessary to achieve protection.
- Immunity and neutralizing antibody responses were dose-dependent.
- Passive transfer of immune plasma conferred protection, confirming the sufficiency of neutralizing antibodies.
- IPV lacking the D antigen component did not induce protection.
- IPV derived from wild-type poliovirus provided superior protection compared to IPV from an attenuated strain.
Conclusions:
- The Tg PVR mouse model is a valuable tool for evaluating IPV potency and efficacy.
- The findings highlight the importance of vaccine formulation and dosage for effective poliovirus immunization.
- This model can aid in developing improved IPV formulations and combination vaccines for childhood immunization schedules.
