Method of producing pharmaceutical compositions comprising immunogenic chikungunya virus CHIKV-Δ5nsP3
Inventors
FRITZER, ANDREA • Meinke, Andreas • Lundberg, Urban • Nebenführ, Mario • HEINDL-WRUSS, Jürgen • Schlegl, Robert • Leon, Arnaud
Assignees
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Publication Number
US-12564625-B2
Publication Date
2026-03-03
Expiration Date
Abstract
The present invention relates to a process for producing an immunogenic live attenuated Chikungunya virus, as well as pharmaceutical compositions comprising the same.
Core Innovation
The invention relates to a pharmaceutical composition comprising chikungunya virus (CHIKV)-ΔnsP3 particles. The composition comprises CHIKV-ΔnsP3 particles that express an E2 structural protein defined by the amino acid sequence of SEQ ID NO: 2, together with a specified proportion of CHIKV-ΔnsP3 particles expressing an E2 structural protein that contains at least one mutation compared with SEQ ID NO: 2.
The at least one E2 mutation is selected from the group consisting of E168K, E247K, H99Y, G55R, H232Y and T230I. The presence and frequency of these E2 mutations are used to maintain desired neutralizing immunogenicity while producing immunogenic live attenuated CHIKV-ΔnsP3 particles.
Serial passaging can increase virus titers while also increasing E2 sequence heterogeneity and can lead to loss of neutralizing immunogenicity. The disclosed relationship links mutation frequency of specific E2 mutations, including E168K, to neutralizing antibody readouts in mouse models using PRNT and VRP-based neutralization assays.
Claims Coverage
The independent claim defines a pharmaceutical composition characterized by CHIKV-ΔnsP3 particles expressing an E2 structural protein defined by SEQ ID NO: 2, together with a specified proportion of particles carrying at least one E2 mutation from a defined set.
CHIKV-ΔnsP3 particles with E2 matching SEQ ID NO: 2
A pharmaceutical composition comprising CHIKV-ΔnsP3 particles, wherein the composition comprises at least 10^3 CHIKV-ΔnsP3 particles which express an E2 structural protein as defined by the amino acid sequence of SEQ ID NO: 2.
Defined E2 mutation set at a controlled particle fraction
The pharmaceutical composition comprises 1–70% CHIKV-ΔnsP3 particles which express an E2 structural protein having at least one mutation compared with the amino acid sequence of SEQ ID NO: 2, wherein the at least one mutation is selected from the group consisting of E168K, E247K, H99Y, G55R, H232Y and T230I.
Overall, the claims focus on a CHIKV-ΔnsP3 pharmaceutical composition with E2 defined by SEQ ID NO: 2, while incorporating a controlled proportion of particles carrying at least one mutation from the specified E2 mutation group.
Stated Advantages
Maintain desired neutralizing immunogenicity while producing immunogenic live attenuated CHIKV-ΔnsP3 particles.
Serial passaging can increase virus titers.
The disclosed relationship links mutation frequency of specific E2 mutations to neutralizing antibody readouts in mouse models using PRNT and VRP-based neutralization assays.
Documented Applications
Mouse models using PRNT and VRP-based neutralization assays.
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