Immunogenic middle east respiratory syndrome coronavirus (MERS-CoV) compositions and methods

An immunogenic and compositional technology, applied in the field of generating high-affinity antibodies, can solve problems such as limiting widespread availability

Active Publication Date: 2016-05-04
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

[0133] Generation of MERSCoV spike nanoparticles

[0134] Nanoparticles were generated by overexpressing the MERSCoV 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

[0136] Induction of immune responses using MERSCoV spike nanoparticles

[0137] 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 with 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

[0139] Potent anti-MERS-CoV human immunoglobulin generated from autotransgenic bovine inhibits MERS-CoV in vivo

[0140] To demonstrate that anti-MERSCoV hIgG antibodies and immunoglobulins obtained from Tc cattle after vaccination can neutralize MERSCoV in vitro and in vivo, we administered three experimental MERSCoV vaccines to three separate Tc cattle herds to induce high titer against MERSCoV neutralizing antibodies. 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-HasaMERS-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-neutralize the virus i...

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Abstract

Disclosed herein are nanoparticles containing MERS virus proteins in polymer structures, and compositions containing the nanoparticles formulated for administration as immunogenic compositions. Also provided herein are vector constructs encoding the proteins, and host cells containing the vector constructs. The disclosure also includes methods of making the nanoparticles and administering them to vertebrates, including methods of inducing immune responses to MERS that reduce or prevent 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). Background of the invention [0005] 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 global h...

Claims

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Application Information

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Patent Type & Authority Applications(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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