Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory symptoms. Due to the lack of medical countermeasures, effective and safe vaccines against MERS-CoV infection are urgently required. Although different types of candidate vaccines have been developed, their immunogenicity is limited, and the dose and administration route need optimization to achieve optimal protection. We here investigated the potential use of human β-defensin 2 (HBD 2) as an adjuvant to enhance the protection provided by MERS-CoV vaccination. We found that immunization of human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice with spike protein receptor-binding domain (S RBD) conjugated with HBD 2 (S RBD-HBD 2) induced potent antigen (Ag)-specific adaptive immune responses and protected against MERS-CoV infection. In addition, immunization with S RBD-HBD 2 alleviated progressive pulmonary fibrosis in the lungs of MERS-CoV-infected hDPP4-Tg mice and suppressed endoplasmic reticulum stress signaling activation upon viral infection. Compared to intramuscular administration, intranasal administration of S RBD-HBD 2 induced more potent mucosal IgA responses and was more effective for protecting against intranasal MERS-CoV infection. In conclusion, our findings suggest that HBD 2 potentiates Ag-specific immune responses against viral Ag and can be used as an adjuvant enhancing the immunogenicity of subunit vaccine candidates against MERS-CoV.

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Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

mBio ◽

10.1128/mbio.00554-20 ◽

2020 ◽

Vol 11 (2) ◽

Cited By ~ 12

Author(s):

Kun Li ◽

Zhuo Li ◽

Christine Wohlford-Lenane ◽

David K. Meyerholz ◽

Rudragouda Channappanavar ◽

...

Keyword(s):

Single Dose ◽

Middle East ◽

Neutralizing Antibody ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

Parainfluenza Virus ◽

Effective Vaccine ◽

Lethal Challenge ◽

Intranasal Immunization ◽

Parainfluenza Virus 5

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection. IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.

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Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice

Veterinary World ◽

10.14202/vetworld.2019.1554-1562 ◽

2019 ◽

Vol 12 (10) ◽

pp. 1554-1562 ◽

Cited By ~ 8

Author(s):

Mustafa Ababneh ◽

Mu'men Alrwashdeh ◽

Mohammad Khalifeh

Keyword(s):

Cell Culture ◽

Middle East ◽

Immune Responses ◽

Protective Antigen ◽

Recombinant Adenovirus ◽

Middle East Respiratory Syndrome ◽

Global Public Health ◽

Cellular Immune Responses ◽

Cellular Immune

Background and Aim: Middle East respiratory syndrome coronavirus (MERS-CoV) has rapidly spread throughout the Middle East since its discovery in 2012. The virus poses a significant global public health threat with potentially devastating effects. In this study, a recombinant adenoviral-based vaccine encoding the spike 1 (S1) subunit of the MERS-CoV genome was constructed, and its humoral, and cellular immune responses were evaluated in mice. Materials and Methods: Mice were immunized initially by intramuscular injection and boosted 3 weeks later by intranasal application. Expression of the S1 protein in the lungs and kidneys was detected using conventional polymerase chain reaction (PCR) and immunohistochemistry (IHC) targeting specific regions within the S1 subunit at weeks 3, 4, 5, and 6 after the first vaccination. Antigen-specific humoral and cellular immune responses were evaluated in serum and in cell culture following in vitro stimulation with a specific 9-mer epitope within the S1 protein (CYSSLILDY). Results: S1 protein expression was only detected by IHC in the kidneys of the Ad-MERS-S1 group at week 6 from first immunization, and in both lungs and kidneys of Ad-MERS-S1 group by conventional PCR at weeks 3 and 5 post-prime. The vaccine elicited a specific S1-immunoglobulin G antibody response, which was detected in the sera of the vaccinated mice at weeks 4 and 6 from the onset of the first immunization. There was a significant increase in the amount of Th1-related cytokines (interferon-γ and interleukin [IL] 12), and a significant decrease in the Th2-related cytokine IL-4 in splenocyte cell culture of the vaccinated group compared with the control groups. Conclusion: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. This study demonstrates a promising vaccine for the control and/or prevention of MERS-CoV infection in humans.

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Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein

Virus Research ◽

10.1016/j.virusres.2014.10.007 ◽

2014 ◽

Vol 194 ◽

pp. 200-210 ◽

Cited By ~ 49

Author(s):

Shuai Xia ◽

Qi Liu ◽

Qian Wang ◽

Zhiwu Sun ◽

Shan Su ◽

...

Keyword(s):

Middle East ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

Entry Inhibitors

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Peptide-Protein Interaction Studies of Antimicrobial Peptides Targeting Middle East Respiratory Syndrome Coronavirus Spike Protein: An In Silico Approach

Advances in Bioinformatics ◽

10.1155/2019/6815105 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Sabeena Mustafa ◽

Hanan Balkhy ◽

Musa Gabere

Keyword(s):

Middle East ◽

Antimicrobial Peptides ◽

Protein Interactions ◽

In Silico ◽

Therapeutic Option ◽

Binding Mode ◽

Middle East Respiratory Syndrome ◽

Spike Protein ◽

In Silico Docking ◽

Peptide Database

There is no effective therapeutic or vaccine for Middle East Respiratory Syndrome and this study attempts to find therapy using peptide by establishing a basis for the peptide-protein interactions through in silico docking studies for the spike protein of MERS-CoV. The antimicrobial peptides (AMPs) were retrieved from the antimicrobial peptide database (APD3) and shortlisted based on certain important physicochemical properties. The binding mode of the shortlisted peptides was measured based on the number of clusters which forms in a protein-peptide docking using Piper. As a result, we identified a list of putative AMPs which binds to the spike protein of MERS-CoV, which may be crucial in providing the inhibitory action. It is observed that seven putative peptides have good binding score based on cluster size cutoff of 208. We conclude that seven peptides, namely, AP00225, AP00180, AP00549, AP00744, AP00729, AP00764, and AP00223, could possibly have binding with the active site of the MERS-CoV spike protein. These seven AMPs could serve as a therapeutic option for MERS and enhance its treatment outcome.

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