Irradiation-inactivated poliovirus, compositions including the same, and methods of preparation
Inventors
Tobin, Gregory J. • Daly, Michael J.
Assignees
Biological Mimetics Inc • Henry M Jackson Foundation for Advancedment of Military Medicine Inc
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Publication Number
US-12042533-B2
Publication Date
2024-07-23
Expiration Date
Abstract
Compositions useful as poliovirus immunogens are provided along with methods and compositions for preparing the same. Compositions comprising poliovirus immunogens can enable a host response that includes virus-neutralizing antibodies which can protect the host from infection and/or disease.
Core Innovation
The invention relates to producing an inactivated poliovirus immunogen by exposing a poliovirus to Mn2+, together with a peptide comprising any one or any combination of SEQ ID NO:1-3, and a phosphate buffer. The poliovirus is then exposed in the presence of the divalent cation, peptide, and buffer to ultraviolet radiation in an amount sufficient to inactivate the poliovirus, thereby providing an inactivated poliovirus immunogen.
The disclosed approach addresses inactivation of poliovirus while maintaining immunogenic properties relevant to neutralizing antibodies. The background problem described in the provided content includes that formalin-inactivated poliovirus immunogens can lose a neutralization epitope associated with VP1, and that there is a biohazard concern related to neuropathogenic strains, motivating alternative inactivation approaches.
The invention also includes inactivation using ionizing radiation and/or ultraviolet radiation in the presence of Mn2+, the selected peptide(s), and phosphate buffer, while controlling air exposure. In particular, the method further includes at least partially replacing air in contact with the poliovirus and/or in a container comprising the poliovirus with a non-reactive gas before the inactivation exposure, producing the inactivated poliovirus immunogen.
Claims Coverage
Two independent claims are provided. Each independent claim defines a production method that uses Mn2+ with a specific peptide set (SEQ ID NO:1-3) in phosphate buffer and then inactivates poliovirus using ultraviolet and/or ionizing radiation, with one claim also requiring non-reactive gas replacement of air.
Mn2+ and SEQ ID NO:1-3 peptide with phosphate buffer followed by UV inactivation yielding a neutralizing-antibody immunogen
A method of producing an inactivated poliovirus immunogen by exposing a poliovirus to Mn2+, a peptide comprising any one or any combination of SEQ ID NO:1-3, and a phosphate buffer, and then exposing the poliovirus in the presence of the divalent cation, peptide, and buffer to ultraviolet radiation in an amount sufficient to inactivate the poliovirus, thereby providing the inactivated poliovirus immunogen that stimulates neutralizing antibodies as determined in the standard Wistar rat model when administered to a subject.
Non-reactive gas replacement of air plus Mn2+ and SEQ ID NO:1-3 peptide with phosphate buffer followed by ionizing/UV inactivation
A method of producing an inactivated poliovirus immunogen by exposing a poliovirus to Mn2+, a peptide comprising any one or any combination of SEQ ID NO:1-3, and a phosphate buffer; at least partially replacing air in contact with the poliovirus and/or in a container comprising the poliovirus with a non-reactive gas; and then exposing the poliovirus to ionizing radiation and/or ultraviolet radiation in an amount sufficient to inactivate the poliovirus, thereby providing the inactivated poliovirus immunogen.
Across the independent claims, the inventive core is the combination of Mn2+ with a peptide comprising SEQ ID NO:1-3 in phosphate buffer during UV and/or ionizing radiation inactivation to generate an inactivated poliovirus immunogen that stimulates neutralizing antibodies, with one claim additionally requiring non-reactive gas replacement of air.
Stated Advantages
Stimulates neutralizing antibodies in the standard Wistar rat model when administered to a subject.
Preserves poliovirus immunogenicity relevant to neutralizing antibodies while inactivating the poliovirus.
Enables inactivation using ionizing radiation and/or ultraviolet radiation in a controlled gas environment by at least partially replacing air with a non-reactive gas.
Documented Applications
Production of irradiation-inactivated poliovirus immunogens (Ir-PV1S/2S/3S) intended to stimulate neutralizing antibodies when administered to a subject, with neutralizing antibody assessment performed using the standard Wistar rat model.
Use of a method to generate inactivated poliovirus immunogen while addressing issues associated with formalin-inactivated poliovirus immunogens, including loss of VP1 neutralization epitope and biohazard concerns related to neuropathogenic strains.
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