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      Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Highlights

          • •

            We compared MERS-CoV RBD-induced immune responses via i.n. and s.c. routes.

          • •

            I.n. induced comparable systemic humoral immune responses as s.c.

          • •

            I.n. induced similar neutralization but more robust cellular responses than s.c.

          • •

            I.n. elicited significantly higher local mucosal immune responses than s.c.

          • •

            Has potential to be developed as an effective and safe MERS mucosal vaccine.

          Abstract

          Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raising a serious concern about its pandemic potential. Therefore, development of effective vaccines is crucial for preventing its further spread and future pandemic. Our previous study has shown that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vaccinated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced systemic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizing antibodies, but more robust systemic cellular immune responses and significantly higher local mucosal immune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD protein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infections caused by MERS-CoV.

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          Most cited references35

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          Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

          Theo M. Bestebroer, Albert Osterhaus, Sander van Boheemen … (2012)
          A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
          Article 0 comments Cited 3033 times – based on 0 reviews     Review now
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            The spike protein of SARS-CoV — a target for vaccine and therapeutic development

            Lanying Du, Yuxian He, Yusen Zhou … (2009)
            Key Points This Review provides an overview on the spike (S) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) as a target for the development of vaccines and therapeutics for the prevention and treatment of SARS. SARS is a newly emerging infectious disease, caused by SARS-CoV, a novel coronavirus that caused a global outbreak of SARS. SARS-CoV S protein mediates binding of the virus with its receptor angiotensin-converting enzyme 2 and promotes the fusion between the viral and host cell membranes and virus entry into the host cell. SARS-CoV S protein induces humoral and cellular immune responses against SARS-CoV. SARS S protein is the target of new SARS vaccines. These vaccines are based on SARS-CoV full-length S protein and its receptor-binding domain, including DNA-, viral vector- and subunit-based vaccines Peptides, antibodies, organic compounds and short interfering RNAs are additional anti-SARS-CoV therapeutics that target the S protein. The work on SARS-CoV S protein-based vaccines and drugs will be useful as a model for the development of prophylactic strategies and therapies against other viruses with class I fusion proteins that can cause emerging infectious diseases.
            Article 0 comments Cited 880 times – based on 0 reviews     Review now
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              Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus

              Abdullah Assiri, Allison McGeer, Trish M. Perl … (2013)
              In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.
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                Author and article information

                Contributors
                Lanying Du
                Shibo Jiang
                Journal
                Journal ID (nlm-ta): Vaccine
                Journal ID (iso-abbrev): Vaccine
                Title: Vaccine
                Publisher: Elsevier Ltd.
                ISSN (Print): 0264-410X
                ISSN (Electronic): 1873-2518
                Publication date PMC-release: 18 February 2014
                Publication date (Print): 11 April 2014
                Publication date (Electronic): 18 February 2014
                Volume: 32
                Issue: 18
                Pages: 2100-2108
                Affiliations
                [a ]Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
                [b ]State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
                [c ]Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
                [d ]Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA
                [e ]Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China
                [f ]Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China
                Author notes
                [* ]Corresponding author. Tel.: +1 212 570 3459; fax: +1 212 570 3299. ldu@ 123456nybloodcenter.org
                [** ]Corresponding author at: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA. Tel.: +1 212 570 3058; fax: +1 212 570 3099. sjiang@ 123456nybloodcenter.org
                [1]

                These authors contributed equally to this work.

                Article
                Publisher ID: S0264-410X(14)00176-5
                DOI: 10.1016/j.vaccine.2014.02.004
                PMC ID: 4194189
                PubMed ID: 24560617
                SO-VID: 4326685a-f93a-40d8-9d85-5ae39c18d78a
                Copyright © Copyright © 2014 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 3 October 2013
                Date revision received : 29 December 2013
                Date accepted : 4 February 2014
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: mers-cov,spike protein,receptor-binding domain,mucosal immune response,systemic immune response,neutralizing antibody
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: mers-cov, spike protein, receptor-binding domain, mucosal immune response, systemic immune response, neutralizing antibody

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