Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein

Alamri, Sawsan S.; Abbas, Ayman T.; Siddiq, Loai A.; Alghamdi, Abrar; Sanki, Mohammad A.; Al-Muhanna, Muhanna K.; Alhabbab, Rowa Yousef; Azhar, Esam I.; Li, Xuguang; Hashem, Anwar M.

doi:10.1038/srep44875

Cited by 89 publications

(87 citation statements)

References 52 publications

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“…Most SARS-CoV and MERS-CoV vaccines developed thus far are based on the inactivated or live attenuated viruses, DNAs, proteins, nanoparticles, viral vectors, including viruslike particles (VLPs) (Zeng et al, 2004;Jiang et al, 2005;Liu et al, 2005;Du et al, 2009aDu et al, , 2016bPimentel et al, 2009;Al-Amri et al, 2017). Each vaccine type has different advantages and disadvantages.…”

Section: Overview Of Vaccines Against Emerging Pathogenic Human Coronmentioning

confidence: 99%

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

et al. 2020

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Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptorbinding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.

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Section: Overview Of Vaccines Against Emerging Pathogenic Human Coronmentioning

confidence: 99%

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

et al. 2020

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“…African Green monkey kidney-derived Vero E6 cells (ATCC #1568) were grown and maintained as previously described (Al-Amri et al, 2017). Human MERS-CoV isolate (MERS-CoV/Hu/Taif/SA/2015) (Al-Amri et al, 2017) was passaged and titrated by tissue culture infection dose 50 (TCID 50 ) assay in Vero E6 cells as previously described (Coleman and Frieman, 2015).…”

Section: Cell Line and Virusmentioning

confidence: 99%

“…Microneutralization assay was performed as previously described (Al-Amri et al, 2017) in the BSL-3 facility at the Special Infectious Agents Unit (SIAU), King Fahd Medical Research Center, King Abdulaziz University. Briefly, heat inactivated serum samples were tested to determine the highest dilution that inhibits cytopathic effect (CPE) of a 100 TCID 50 of MERS-CoV/Hu/Taif/SA/2015 in Vero E6 cells.…”

Section: Mn Assaymentioning

confidence: 99%

Development and validation of different indirect ELISAs for MERS-CoV serological testing

Hashem

Alamri

Alsubhi

et al. 2019

Journal of Immunological Methods

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Since 2012, MERS-CoV has caused up to 2220 cases and 790 deaths in 27 countries with Saudi Arabia being the most affected country with~83.1% of the cases and~38.8% local death rate. Current serological assays such as microneutralization (MN), plaque reduction neutralization, immunofluorescence, protein microarray or pseudoparticle neutralization assays rely on handling of live MERS-CoV in high containment laboratories or need for expensive and special equipment and reagents and highly trained personnel which represent a technical hurdle for most laboratories in resource-limited MERS-CoV endemic countries. Here, we developed, compared and evaluated three different indirect ELISAs based on MERS-CoV nucleocapsid protein (N), spike (S) ectodomain (amino acids 1-1297) and S1 subunit (amino acids 1-725) and compared them with MN assay. The developed ELISAs were evaluated using large number of confirmed seropositive (79 samples) and seronegative (274 samples) MERS-CoV human serum samples. Both rS1-and rS-ELISAs maintained high sensitivity and specificity (≥90%) across a wider range of OD values compared to rN-ELISA. Moreover, rS1-and rS-based ELISAs showed better agreement and correlation with MN assay in contrast to rN-ELISA. Collectively, our data demonstrate that rS1-ELISA and rS-ELISA are more reliable than rN-ELISA and represent a suitable choice for seroepidemiological testing and surveillance in MERS-CoV endemic regions. Several MERS-CoV serological assays have been developed and https://doi.

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“…MERS-CoV causes a wide range of manifestations ranging from asymptomatic infections to mild or severe respiratory disease. Detection of anti-MERS-CoV antibodies (Abs) in humans and/or animals represents a valuable tool in diagnostics as well as epidemiological, virological, and immunological studies including evaluation of vaccine immunogenicity [4][5][6][7][8]. Several serological assays have been developed and used for MERS-CoV, including ELISAbased assays, immunofluorescence assays, protein microarrays, and pseudovirus-based neutralization assays [9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of MERS-CoV Neutralizing Antibodies in Sera Using Live Virus Microneutralization Assay

Algaissi

Hashem

2019

Methods in Molecular Biology

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The microneutralization (MN) assay is a standard and important technique in virology, immunology, and epidemiology. It is a highly specific and sensitive assay for evaluating virus-specific neutralizing antibodies (nAbs) in human and animal sera. It provides the most precise answer to whether or not an individual or animal has antibodies that can neutralize or inhibit the infectivity of a specific virus strain. However, using live virus-based MN assay might require working under high containment facilities especially when dealing with high-risk pathogens such as the Middle East respiratory syndrome-coronavirus (MERS-CoV). In this chapter, we describe the isolation, amplification, and titration of MERS-CoV, as well as detailed MN assay to measure nAb levels in sera from different mammalian species.

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Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein

Cited by 89 publications

References 52 publications

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

Development and validation of different indirect ELISAs for MERS-CoV serological testing

Evaluation of MERS-CoV Neutralizing Antibodies in Sera Using Live Virus Microneutralization Assay

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