Immunogenic composition forming a SARS-CoV-2 vaccine, and a method for its manufacture
Inventors
Mosharraf, Mitra • Sorayya, Aryo • Nayar, Rajiv
Assignees
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Publication Number
US-11278617-B2
Publication Date
2022-03-22
Expiration Date
Abstract
An immunogenic composition forming a vaccine includes a nanoparticle adjuvant comprising at least a nanoparticle, wherein the at least a nanoparticle comprises a lipid layer exterior including a plurality of lipids, cholesterol, and a primary alkyl amine including a positively charged amino group head and at least a carbon tail and an antigen incorporated in the at least a nanoparticle, wherein the antigen comprises a spike protein from a coronavirus.
Core Innovation
An immunogenic composition forming a vaccine is described as including an immunogenic SARS-CoV-2 spike protein antigen combined with a lipid-layer nanoparticle adjuvant having a lipid layer exterior. The lipid layer exterior includes DPPC, DOPC, cholesterol, and a primary alkyl amine that includes a positively charged amino group head with a carbon tail. The DPPC:DOPC:cholesterol:alkyl amine molar ratio is specified as 40:20-30:20:10-30.
The antigen comprises a spike protein from SARS-CoV-2, including SARS-CoV-2 spike protein structures such as S, S1/S2 (trimeric spike), and related spike components such as S1 and S2. Incorporation of the spike-protein antigen into or with the nanoparticle adjuvant is described as being achieved by lyophilizing the nanoparticle adjuvant, then combining the antigen with a buffer to form a suspension, and reconstituting the nanoparticle adjuvant with the suspension.
The described manufacturing approach emphasizes lyophilizing the nanoparticle adjuvant and then reconstituting it with an antigen-containing suspension to produce the immunogenic vaccine composition. Lyophilized manufacture/reconstitution is also described with optional lyoprotectants, and delivery formats are included. Stability is described for lyophilized formulations, including maintaining particle size and UV absorbance at elevated temperature.
Claims Coverage
One independent claim is explicitly provided, covering a manufacturing method for an immunogenic composition forming a vaccine. The claim includes three main inventive feature groups: a specific lipid-layer nanoparticle adjuvant composition and ratios, inclusion of a SARS-CoV-2 spike antigen, and a lyophilization plus reconstitution manufacturing sequence.
Lipid-layer nanoparticle adjuvant with specified DPPC:DOPC:cholesterol:alkyl amine ratio
A nanoparticle adjuvant comprising at least one nanoparticle having a lipid layer exterior with at least one lipid, where the lipid layer exterior further comprises DPPC, DOPC, cholesterol, and a primary alkyl amine including a positively charged amino group head and at least a carbon tail, with the DPPC:DOPC:cholesterol:alkyl amine molar ratio being 40:20-30:20:10-30.
SARS-CoV-2 spike protein antigen as provided antigen
Providing an antigen comprising a spike protein from SARS-CoV-2.
Lyophilize nanoparticle adjuvant and reconstitute with antigen suspension
Combining the antigen with the nanoparticle adjuvant, wherein combining comprises lyophilizing the nanoparticle adjuvant, combining the antigen with a buffer to form a suspension, and reconstituting the nanoparticle adjuvant with the suspension.
Across the provided independent claim, coverage is centered on a lipid-layer nanoparticle adjuvant having a specified DPPC:DOPC:cholesterol:primary alkyl amine composition and molar ratio, pairing the adjuvant with a SARS-CoV-2 spike protein antigen, and producing the vaccine composition by lyophilizing the adjuvant and reconstituting it with an antigen-containing buffered suspension.
Stated Advantages
Lyophilized formulations maintain particle size stability and UV absorbance stability at elevated temperature.
Documented Applications
Manufacture of an immunogenic SARS-CoV-2 (coronavirus) vaccine composition.
Mouse immunization studies are described, including measurement of ELISA IgG endpoint titer against SARS-CoV-2 spike proteins using formulations A/B/D.
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