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Vaccine. Intranasal vaccination with recombinant RBD of MERS-CoV s-protein induces much stronger local mucosal immune responses than subcutaneous immunization...
[Source: Vaccine, full page: (LINK). Abstract, edited.]
Vaccine, Available online 18 February 2014 / In Press, Uncorrected Proof
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
Cuiqing Ma<SUP>a</SUP><SUP>, </SUP><SUP>f</SUP><SUP>, </SUP><SUP>1</SUP>, Ye Li<SUP>a</SUP><SUP>, </SUP><SUP>1</SUP>, Lili Wang<SUP>a</SUP>, Guangyu Zhao<SUP>b</SUP>, Xinrong Tao<SUP>c</SUP>, Chien-Te K. Tseng<SUP>c</SUP><SUP>, </SUP><SUP>d</SUP>, Yusen Zhou<SUP>b</SUP>, Lanying Du<SUP>a</SUP>, Shibo Jiang<SUP>a</SUP><SUP>, </SUP><SUP>e</SUP>
<SUP>_____</SUP>
<SUP></SUP>
<SUP>a</SUP> Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA; <SUP>b</SUP> State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; <SUP>c</SUP> Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; <SUP>d</SUP> Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA; <SUP>e</SUP> Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China; <SUP>f</SUP> Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China
Received 3 October 2013, Revised 29 December 2013, Accepted 4 February 2014, Available online 18 February 2014
______
Highlights
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.
Keywords
MERS-CoV; Spike protein; Receptor-binding domain; Mucosal immune response; Systemic immune response; Neutralizing antibody
Corresponding author. Tel.: +1 212 570 3459; fax: +1 212 570 3299.
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.
1) These authors contributed equally to this work.
Copyright ? 2014 Published by Elsevier Ltd.
Note to users: Uncorrected proofs are Articles in Press that have been copy edited and formatted, but have not been finalized yet. They still need to be proof-read and corrected by the author(s) and the text could still change before final publication.
Although uncorrected proofs do not have all bibliographic details available yet, they can already be cited using the year of online publication and the DOI, as follows: author(s), article title, journal (year), DOI. Please consult the journal's reference style for the exact appearance of these elements, abbreviation of journal names and use of punctuation.
When the final article is assigned to an issue of the journal, the Article in Press version will be removed and the final version will appear in the associated published issue of the journal. The date the article was first made available online will be carried over.
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Vaccine, Available online 18 February 2014 / In Press, Uncorrected Proof
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
Cuiqing Ma<SUP>a</SUP><SUP>, </SUP><SUP>f</SUP><SUP>, </SUP><SUP>1</SUP>, Ye Li<SUP>a</SUP><SUP>, </SUP><SUP>1</SUP>, Lili Wang<SUP>a</SUP>, Guangyu Zhao<SUP>b</SUP>, Xinrong Tao<SUP>c</SUP>, Chien-Te K. Tseng<SUP>c</SUP><SUP>, </SUP><SUP>d</SUP>, Yusen Zhou<SUP>b</SUP>, Lanying Du<SUP>a</SUP>, Shibo Jiang<SUP>a</SUP><SUP>, </SUP><SUP>e</SUP>
<SUP>_____</SUP>
<SUP></SUP>
<SUP>a</SUP> Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA; <SUP>b</SUP> State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; <SUP>c</SUP> Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; <SUP>d</SUP> Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA; <SUP>e</SUP> Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China; <SUP>f</SUP> Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, China
Received 3 October 2013, Revised 29 December 2013, Accepted 4 February 2014, Available online 18 February 2014
______
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.
Keywords
MERS-CoV; Spike protein; Receptor-binding domain; Mucosal immune response; Systemic immune response; Neutralizing antibody
Corresponding author. Tel.: +1 212 570 3459; fax: +1 212 570 3299.
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.
1) These authors contributed equally to this work.
Copyright ? 2014 Published by Elsevier Ltd.
Note to users: Uncorrected proofs are Articles in Press that have been copy edited and formatted, but have not been finalized yet. They still need to be proof-read and corrected by the author(s) and the text could still change before final publication.
Although uncorrected proofs do not have all bibliographic details available yet, they can already be cited using the year of online publication and the DOI, as follows: author(s), article title, journal (year), DOI. Please consult the journal's reference style for the exact appearance of these elements, abbreviation of journal names and use of punctuation.
When the final article is assigned to an issue of the journal, the Article in Press version will be removed and the final version will appear in the associated published issue of the journal. The date the article was first made available online will be carried over.
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