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Immunogenic Middle East respiratory syndrome coronavirus (mers-cov) compositions and methods

A technology of immunogenicity and composition, applied in the field of generating high-affinity antibodies, which can solve problems such as limiting wide availability

Active Publication Date: 2019-12-03
NOVAVAX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, generation of large quantities of anti-pathogen human plasma and / or immunoglobulins with high affinity and avidity antibodies currently requires donations from convalescent patients, which limits the widespread availability of these human-derived products for a number of cultural, infrastructural and logistical reasons Spend

Method used

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  • Immunogenic Middle East respiratory syndrome coronavirus (mers-cov) compositions and methods
  • Immunogenic Middle East respiratory syndrome coronavirus (mers-cov) compositions and methods
  • Immunogenic Middle East respiratory syndrome coronavirus (mers-cov) compositions and methods

Examples

Experimental program
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Effect test

Embodiment 1

[0137] Generation of MERS CoV spike nanoparticles

[0138] Nanoparticles were generated by overexpressing the MERS CoV spike protein in baculovirus (Figures 8 and 9) in Sf9 cells. After purification, spike protein-containing nanoparticle VLPs were mainly recovered as trimers ( Figure 4 and 6 ).

Embodiment 2

[0140] Induction of immune responses using MERS CoV spike nanoparticles

[0141] Administration of VLPs to mice, such as Figure 5 displayed in . At the end of the 45 day period, blood was drawn from the mice to assess the immune response. Figure 7 Neutralizing antibody titers of mice administered SARS CoV spike nanoparticle VLPs or MERS CoV spike nanoparticle VLPs are shown. The highest response was obtained by using the adjuvant matrix M1.

Embodiment 3

[0143] Potent anti-MERS-CoV human immunoglobulin generated from autotransgenic bovine inhibits MERS-CoV in vivo

[0144] To demonstrate that anti-MERS CoV hIgG antibodies and immunoglobulins obtained from Tc cattle following vaccination can neutralize MERS CoV in vitro and in vivo, we administered three experimental MERS CoV vaccines to three separate Tc cattle herds to induce resistance to High-titer neutralizing antibodies to MERS CoV. The first vaccine tested was a whole killed Jordan strain (clade A) MERS-CoV virion (WKV) vaccine and the second was an Al-Hasa (clade B) MERS-CoV spike nanoparticle (SN ) vaccine, while the third is the Al-Hasa MERS-CoV spike protein pDNA vaccine. The pDNA vaccine was found to be poorly immunogenic by in vitro assays and was not evaluated further (data not presented). However, convalescent sera and highly purified hIgG immunoglobulins from both WKV (designated SAB-300) and SN (designated SAB-301) vaccinated Tc cattle were able to cross-neut...

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Abstract

Disclosed herein are nanoparticles containing MERS virus proteins in a multimeric structure, and compositions containing the nanoparticles formulated for administration in immunogenic compositions. Also provided herein is a vector construct encoding the protein, and a host cell containing the vector construct. The disclosure also includes methods of producing the nanoparticles and administering them to vertebrates, including methods of inducing an immune response against MERS that reduces or prevents infection by the virus.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 61 / 880,111 filed September 19, 2013, which is hereby incorporated by reference in its entirety for all purposes. [0003] Description of electronically submitted text files [0004] The contents of the text file electronically filed with this article are incorporated in its entirety by reference: Computer-readable copy of the sequence listing (file name: NOVV-056 / 01WO_Seqlist.txt, date of record: September 18, 2014, file size : 17,384 megabytes). [0005] Background of the invention [0006] Coronaviruses can cause disease in animals such as humans. SARS (Severe Acute Respiratory Syndrome) is an example of such a disease. Recently, a new coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), has emerged and has been associated with human deaths. MERS-CoV has been identified by the World Health Organization (WHO) as a "threat to ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/215
CPCA61K39/12A61K2039/5258C12N2770/20034A61P31/14A61K39/215A61K39/42A61K2039/505A61K2039/552A61K2039/575C07K14/005C07K16/10C07K2317/92C12N7/00C12N2770/20022C12N2770/20071
Inventor G·史密斯Y·刘M·马萨尔
Owner NOVAVAX
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