MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

Coleman, Christopher M.; Venkataraman, Thiagarajan; Liu, Ye V.; Glenn, Gregory M.; Smith, Gale; Flyer, David C.; Frieman, Matthew B.

doi:10.1016/j.vaccine.2017.02.012

Cited by 87 publications

(92 citation statements)

References 19 publications

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“…Therefore, there has been much research on how to present effectively the main target antigen, spike protein. Previous studies have reported the effectiveness of DNA vaccines containing the spike protein gene [18,19], spike protein itself [13,17], RBD subunit vaccines [14][15][16], and viral vectors including modified vaccinia virus Ankara and adenovirus [8][9][10][11][12] for immunization of mice or nonhuman primates. Subunit vaccines, such as spike protein and RBD protein, induced neutralizing antibody against MERS-CoV, indicating the induction of a humoral immune response, and the DNA vaccine triggered the activation of cytotoxic T cells, indicating the induction of a cellular immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Although several approaches to developing a MERS-CoV vaccine have been reported, there is no clinically approved vaccine for MERS-CoV. Previous studies have investigated viral vector-based vaccines [8][9][10][11][12], subunit vaccines [13][14][15][16][17], and DNA vaccines [18,19]. Of these, vaccination using viral vectors or DNA immunization successfully generated neutralizing antibodies and protected against infection [12].…”

Section: Introductionmentioning

confidence: 99%

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Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

Jung

Kang

Lee

et al. 2018

Vaccine

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The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS. Although both types of vaccine could induce specific immunoglobulin G against MERS-CoV, neutralizing antibodies against MERS-CoV were induced only by heterologous prime-boost immunization and homologous immunization with spike protein nanoparticles. Interestingly, Th1 cell activation was induced by immunization schedules including Ad5/MERS, but not by those including only spike protein nanoparticles. Heterologous prime-boost vaccination regimens including Ad5/MERS elicited simultaneous Th1 and Th2 responses, but homologous prime-boost regimens did not. Thus, heterologous prime-boost may induce longer-lasting immune responses against MERS-CoV because of an appropriate balance of Th1/Th2 responses. However, both heterologous prime-boost and homologous spike protein nanoparticles vaccinations could provide protection from MERS-CoV challenge in mice. Our results demonstrate that heterologous immunization by priming with Ad5/MERS and boosting with spike protein nanoparticles could be an efficient prophylactic strategy against MERS-CoV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

Jung

Kang

Lee

et al. 2018

Vaccine

View full text Add to dashboard Cite

show abstract

“…The Spike gene plays a significant role in host cell attachment and the entry of the virus in the host cells [23]. The RBD of Spike protein gene mediates the virus interaction to the host cell and binds with dipeptidyl peptidase 4 (DPP4, CD26) known as a cellular receptor which favors the viral entry into the cell and is immunodominant and induces neutralizing antibodies [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity of MERS-CoV spike protein gene in Saudi Arabia

Sohrab¹,

Azhar²

2020

Journal of Infection and Public Health

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a b s t r a c tBackground: Middle East respiratory syndrome coronavirus (MERS-CoV) was primarily detected in 2012 and still causing disease in human and camel. Camel and bats have been identified as a potential source of virus for disease spread to human. Although, significant information related to MERS-CoV disease, spread, infection, epidemiology, clinical features have been published, A little information is available on the sequence diversity of Spike protein gene. The Spike protein gene plays a significant role in virus attachment to host cells. Recently, the information about recombinant MERS-CoV has been published. So, this work was designed to identify the emergence of any another recombinant virus in Jeddah, Saudi Arabia. Methods: In this study samples were collected from both human and camels and the Spike protein gene was amplified and sequenced. The nucleotide and amino acid sequences of MERS-CoV Spike protein gene were used to analyze the recombination, genetic diversity and phylogenetic relationship with selected sequences from Saudi Arabia. Results: The nucleotide sequence identity ranged from 65.7% to 99.8% among all the samples collected from human and camels from various locations in the Kingdom. The lowest similarity (65.7%) was observed in samples from Madinah and Dammam. The phylogenetic relationship formed different clusters with multiple isolates from various locations. The sample collected from human in Jeddah hospital formed a closed cluster with human samples collected from Buraydah, while camel sample formed a closed cluster with Hufuf isolates. The phylogenetic tree by using Aminoacid sequences formed closed cluster with Dammam, Makkah and Duba isolates. The amino acid sequences variations were observed in 28/35 samples and two unique amino acid sequences variations were observed in all samples analyzed while total 19 nucleotides sequences variations were observed in the Spike protein gene. The minor recombination events were identified in eight different sequences at various hotspots in both human and camel samples using recombination detection programme. Conclusion: The generated information from this study is very valuable and it will be used to design and develop therapeutic compounds and vaccine to control the MERS-CoV disease spread in not only in the Kingdom but also globally.

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“…95 Currently a variety of adjuvants have been investigated for MERS-CoV vaccines: alum, MF59, Matrix-M1, CpG, and Poly (I:C). 67,71,75,96 The use of adjuvants such as alum, CpG, and delta-inulin-based polysaccharide adjuvant has been shown to increase NAb titers and ameliorate lung eosinophilic immunopathology, 95,97 suggesting that adjuvants may be utilized in MERS-CoV vaccine development to improve immunogenicity and safety.…”

Section: Discussionmentioning

confidence: 99%

“…70 MERS-CoV S protein nanoparticles have also been developed as a possible vaccine candidate. Coleman et al 74,75 demonstrated that recombinant MERS-CoV S nanoparticles in combination with Matrix-M1 adjuvant induced NAbs, reduced lung viral titers and MERS-CoV M mRNA to baseline levels in transduced mice, suggesting that MERS-CoV replication was efficiently blocked. Matrix-M is a saponin-based adjuvant which has been shown to enhance humoral, cellular and protective responses with various pathogen vaccines including a H7N9 vaccine and Ebola virus vaccine.…”

Section: Protein Subunit Vaccinesmentioning

confidence: 99%

Development of Middle East Respiratory Syndrome Coronavirus vaccines – advances and challenges

Cho

Excler

Kim

et al. 2017

Human Vaccines & Immunotherapeutics

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Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging pathogen with the potential to pose a threat to global public health. Sporadic cases and outbreaks continue to be reported in the Middle East, and case fatality rates remain high at approximately 36% globally. No specific preventive or therapeutic countermeasures currently exist. A safe and effective vaccine could play an important role in protecting against the threat from MERS-CoV. This review discusses human vaccine candidates currently under development, and explores viral characteristics, molecular epidemiology and immunology relevant to MERS-CoV vaccine development. At present, a DNA vaccine candidate has begun a human clinical trial, while two vector-based candidates will very soon begin human trials. Protein-based vaccines are still at pre-clinical stage. Challenges to successful development include incomplete understanding of viral transmission, pathogenesis and immune response (in particular at the mucosal level), no optimal animal challenge models, lack of standardized immunological assays, and insufficient sustainable funding.

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MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

Cited by 87 publications

References 19 publications

Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

Genetic diversity of MERS-CoV spike protein gene in Saudi Arabia

Development of Middle East Respiratory Syndrome Coronavirus vaccines – advances and challenges

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