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EP-4735467-A1 - SARS-COV-2 PROTEIN EPITOPES AND USE THEREOF IN PREVENTION AND DIAGNOSIS OF CORONAVIRUS INFECTIONS

EP4735467A1EP 4735467 A1EP4735467 A1EP 4735467A1EP-4735467-A1

Abstract

The subject of the invention are novel peptides derived from SARS-CoV-2 coronavirus proteins, the peptides being immunoreactive epitopes that interact with convalescent serum, use thereof in prevention and diagnosis of SARS-CoV-2 infections, and an innovative SARS-CoV-2 vaccine, comprising immunoreactive peptides and a thermostable nanoadjuvant that enables effective intranasal administration.

Inventors

  • GÓRSKA, Sabina
  • RAZIM, Agnieszka
  • ORZECHOWSKA, Beata
  • GAMIAN, ANDRZEJ

Assignees

  • Instytut Immunologii I Terapii Doswiadczalnej Im.Ludwika Hirszfelda Pan We Wroclawiu

Dates

Publication Date
20260506
Application Date
20240701

Claims (11)

  1. 1. A SARS-CoV-2 protein peptide having sequence selected from: SEQ NO 1, SEQ NO 2, SEQ NO 3, SEQ NO 4 or SEQ NO 5.
  2. 2. The peptide of claim 1 , characterized in that it is conjugated to a carrier protein.
  3. 3. The peptide of claim 2, characterized in that the carrier protein is KLH or TT or identical.
  4. 4. The peptide of claim 1 , characterized in that the peptides are produced synthetically or by recombination.
  5. 5. The SARS-CoV-2 protein peptide as defined in claims 1-3 for use in inducing immunological response against SAR-CoV-2 virus in a patient, prevention and treatment of COVID-19 disease caused by SAR-CoV-2 coronavirus infection.
  6. 6. The peptide for use as defined in claim 5 for intranasal administration.
  7. 7. A vaccine composition comprising the peptide as defined in one of claims 1-3 and a pharmaceutically acceptable carrier and/or adjuvant or nanoadjuvant.
  8. 8. The vaccine composition of claim 7, characterized in that the nanoadjuvant comprises 65% emulsified soybean oil, 8% ethanol, 21 % water, 5% Tyloxapol, 1 % benzalkonium chloride.
  9. 9. The vaccine composition as defined in one of claims 5-6 for use in inducing immunological response against SAR-CoV-2 virus in a patient, prevention and treatment of COVID-19 disease caused by SAR-CoV-2 coronavirus infection.
  10. 10. The vaccine composition for use as defined in claim 8, characterized in that it is administered intranasally.
  11. 11. A method for detecting a coronavirus infection, in particular SARS-CoV-2 infection, characterized in that (c) the peptide as defined in claim 1 is provided, SUBSTITUTE SHEET (RULE 26) (d) the peptide as defined in claim 1 is contacted with a biological sample from a patient, e.g. blood and saliva, (e) presence of complexes of the peptide as defined in claim 1 with antibodies specific to the peptide as defined in claim 1 is detected, wherein the presence of such complexes is indicative of the patient being infected with the virus. SUBSTITUTE SHEET (RULE 26)

Description

SARS-CoV-2 protein epitopes and use thereof in prevention and diagnosis of coronavirus infections The subject of the invention are novel peptides derived from SARS-CoV-2 coronavirus proteins, said peptides being immunoreactive epitopes intereacting with convalescent serum, use thereof in the prevention and diagnosis of SARS-CoV-2 infections, and an innovative SARS-CoV-2 vaccine, comprising immunoreactive peptides and a thermostable nanoadjuvant enabling effective intranasal administration. State of the art According to the data collected by the World Health Organization (WHO) in 2022, the COVID-19 pandemic resulted in more than 450 million cases worldwide and more than 6 million deaths. COVID-19 is a disease caused by the SARS-CoV-2 coronavirus, which is characterized by rapid spread and a high mutation rate. SARS-CoV-2 is a typical mucosal pathogen that is transmitted from person to person via droplet route. It infects human respiratory epithelial cells, binding to angiotensin-converting enzyme 2 (ACE2) receptors via the viral receptor-binding domain (RBD). The development of highly effective COVID-19 vaccines played a pivotal role in controlling and preventing the pandemic. The vaccines are based on 5 main platforms: messenger RNA (mRNA), viral vector, inactivated virus, subunit (consisting of proteins or peptides), and DNA [WHO R&D Blueprint Team. COVID-19 Vaccine Tracker and Landscape. World Health Organisation 2021. https://www.who. int/covid-19/vaccinesl. Spike protein (S protein), located outside the virion, is the primary antigen in vaccines against COVID-19. It is an effective target for neutralizing antibodies that block and prevent S binding to ACE2 receptors on host cells or S rearrangement, thus preventing the virus entry. Different S protein domains are used as vaccine antigens, e.g. N-terminal domain (NTD) or RBD [Buchholz UJ, Bukreyev A, Yang L et al. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci USA 2004;101 :9804-9], For example, the BNT162b2 vaccine (developed by Pfizer and BioNTech) and the mRNA-1273 vaccine (developed by Moderna) consist of mRNA surrounded by lipid nanoparticles. mRNA is injected intramuscularly, where it is taken up by host cells and translated. Due to the relative fragility of mRNA, it needs to be stored in very low temperatures. Such requirements impede the manufacturing, storage and distribution of vaccines. mRNA is also less stable in vivo, which often requiring the development of stabilizing elements, e.g. base modification to incorporate N1 -methyl-pseudouridine (ml ^P). Viral vector vaccines use genetically modified virus which infects human cells. S protein gene of SARS-CoV-2 is inserted into a non-human adenoviral vector. For instance, Vaxzevria vaccine (developed by AstraZeneca and University of Oxford) comprises ChAdOxI chimpanzee adenovirus, with a replication defect caused by E1 and E3 deletion. The S protein gene embedded in the vector has optimized codons with tissue plasminogen activator (tPA) leader sequence [Voysey M, Clemens SAC, Madhi SA et al. Safety and efficacy of the ChAdOxI nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021 ;397:99-111 ], Next, NVX-CoV2373 vaccine (Nuvaxovid) developed by Novavax is a subunit vaccine comprising a full-length recombinant trimeric perfusion S protein (SARS- CoV-2-3Q-2P) and a saponin-based Matrix-M nanoadjuvant. The protein was produced by recombination using protein expression in insect cells with the baculovirus system [Paul T. Heath et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med 2021 ; 385:1172-1183 DOI: 10.1056/NEJMoa2107659], Mucosal immunity is essential for adequate and long-lasting protection against a viral infection. All licensed COVID-19 vaccines are administered via intramuscular injection, being ineffective in inducing mucosal immunity. They do not prevent upper respiratory track viral infections, which in part due to a failure to activate mucosal immunity. Furthermore, emerging novel SARS-CoV-2 variants highlights the need for the next generation of vaccines against COVID- 19, and intranasal vaccination method is highly desirable for effective induction of both mucosal and systemic immune response. As many as 7 different intranasal vaccines are currently being tested in clinical studies [Carl Zimmer, Jonathan Corum, Sui-Lee Wee, Coronavirus Vaccine Tracker, https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-t, Yury Valdes-Balbin, Darielys Santana-Mederos, Lauren Quintero, Sonsire Fernandez, Laura Rodriguez, Belinda Sanchez Ramirez, Rocmira Perez-Nicado, Claudia Acosta, Yanira Mendez, Manuel G. Ricardo, Tays Hernandez, Gretchen Bergado, Franciscary Pi, Annet Valdes, Tania Carmenate, Ubel Ramirez, Reinaldo Oliva, Jean-Pierre Soubal, Raine Garrido, Felix Cardoso, Mario L