Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Adney, Danielle R.; Wang, Lingshu; Doremalen, Neeltje van; Shi, Wei; Zhang, Yi; Kong, Wing-Pui; Miller, Megan R.; Bushmaker, Trenton; Scott, Dana; Wit, Emmie de; Modjarrad, Kayvon; Petrovsky, Nikolai; Graham, Barney S.; Bowen, Richard A.; Munster, Vincent J.

doi:10.3390/v11030212

Cited by 82 publications

(97 citation statements)

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“…It has been shown that a MERS-CoV S1 protein formulated with Ribi (for mice) or aluminum phosphate (for NHPs) adjuvant elicited robust neutralizing antibodies in mice and NHPs against divergent strains of pseudotyped and live MERS-CoV, protecting NHPs from MERS-CoV infection . In addition, MERS-CoV S1 protein adjuvanted with Advax and Sigma Adjuvant System induced low-titer neutralizing antibodies in dromedary camels with reduced and delayed viral shedding after MERS-CoV challenge, but high-titer neutralizing antibodies in alpacas with complete protection of viral shedding from viral infection, indicating that protection of MERS-CoV infection is positively correlated with serum neutralizing antibody titers (Adney et al, 2019). Moreover, immunization with a recombinant MERS-CoV NTD protein (rNTD) can induce neutralizing antibodies and cellmediated responses, protecting Ad-hDPP4-transduced mice against MERS-CoV challenge (Jiaming et al, 2017).…”

Section: Mers-cov Subunit Vaccines Based On Non-rbd S Protein Fragmentsmentioning

confidence: 97%

“…Therefore, these vaccines may generate potent neutralizing antibodies with strong protective immunity against viral infection. S1 subunit, for example, is much shorter than the full-length S protein, but it is no less able to induce strong immune responses and/or protection against viral infection Adney et al, 2019). Thus, this fragment can be used as an alternative target for subunit vaccine development.…”

Section: Potential Targets For Development Of Sars-cov and Mers-cov Smentioning

confidence: 99%

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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: Mers-cov Subunit Vaccines Based On Non-rbd S Protein Fragmentsmentioning

confidence: 97%

Section: Potential Targets For Development Of Sars-cov and Mers-cov Smentioning

confidence: 99%

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

et al. 2020

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“…Although it seems that the ultimate origin of MERS-CoV was from bats (6), there are still significant differences between the genome sequences of these betacoronaviruses in bats from the subgenus Merbecovirus and MERS-CoV, suggesting that interspecies jumping from bats to camels may not be a very recent event, and hence the dromedaries are probably the reservoir of MERS-CoV where the virus was transmitted to humans. In the last few years, a number of MERS-CoV vaccines have been developed for their potential use in dromedaries (19)(20)(21)(22)(23). In this study, our results indicated that Bactrian and hybrid camels are also potential sources of MERS-CoV infection.…”

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confidence: 55%

Middle East Respiratory Syndrome Coronavirus Antibodies in Bactrian and Hybrid Camels from Dubai

Lau

Luk

et al. 2020

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So far, dromedary camels are the only known animal reservoir for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). Previous published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies. However, a recent study revealed that direct inoculation of Bactrian camels intranasally with MERS-CoV can lead to infection with abundant virus shedding and seroconversion. In this study, we examined the presence of MERS-CoV antibodies in Bactrian and hybrid camels in Dubai, the United Arab Emirates (where dromedaries are also present), and Bactrian camels in Xinjiang, China (where dromedaries are absent). For the 29 serum samples from Bactrian camels in Dubai tested by the MERS-CoV spike (S) protein-based enzyme-linked immunosorbent assay (S-ELISA) and neutralization antibody test, 14 (48%) and 12 (41%), respectively, were positive for MERS-CoV antibodies. All the 12 serum samples that were positive with the neutralization antibody test were also positive for the S-ELISA. For the 11 sera from hybrid camels in Dubai tested with the S-ELISA and neutralization antibody test, 6 (55%) and 9 (82%), respectively, were positive for MERS-CoV antibodies. All the 6 serum samples that were positive for the S-ELISA were also positive with the neutralization antibody test. There was a strong correlation between the antibody levels detected by S-ELISA and neutralizing antibody titers, with a Spearman coefficient of 0.6262 (P Ͻ 0.0001; 95% confidence interval, 0.5062 to 0.7225). All 92 Bactrian camel serum samples from Xinjiang were negative for MERS-CoV antibodies tested using both S-ELISA and the neutralization antibody test. Bactrian and hybrid camels are potential sources of MERS-CoV infection. IMPORTANCE Since its first appearance in 2012, Middle East respiratory syndrome (MERS) has affected Ͼ25 countries, with Ͼ2,400 cases and an extremely high fatality rate of Ͼ30%. The total number of mortalities due to MERS is already greater than that due to severe acute respiratory syndrome. MERS coronavirus (MERS-CoV) has been confirmed to be the etiological agent. So far, dromedaries are the only known animal reservoir for MERS-CoV. Previously published serological studies showed that sera of Bactrian camels were all negative for MERS-CoV antibodies. In this study, we observed that 41% of the Bactrian camel sera and 55% of the hybrid camel sera from Dubai (where dromedaries are also present), but none of the sera from Bactrian camels in Xinjiang (where dromedaries are absent), were positive for MERS-CoV antibodies. Based on these results, we conclude that in addition to dromedaries, Bactrian and hybrid camels are also potential sources of MERS-CoV infection.

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“…This is likely related to a traditional phenomenon, namely self-limitation or resolution, in which the neutralizing antibodies titer is decreased following the booster immunization as a response to the administrated antigens [24,25]. Several studies showed that the protective efficacy of MERS-CoV vaccines positively correlates with the evoked neutralizing antibody titers in the serum of vaccinated animals [26,27]. These results are in accordance with the results of other viral platforms chimeric viruses carrying spike protein which provided nAbs against MERS-CoV [9,28].…”

Section: Discussionmentioning

confidence: 99%

A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice

et al. 2019

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Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736-761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses. Software, M.M.S.; Formal Analysis and Investigation, M.M.S., A.K., A.M., R.E.-S., G.K. and M.A.A.; Writing-Original Draft Preparation, M.Supervision, G.K and M.A.A.; Funding acquisition R.W., G.K., M.A.A.; all authors revised and approved the final manuscript.

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Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

Cited by 82 publications

References 37 publications

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses

Middle East Respiratory Syndrome Coronavirus Antibodies in Bactrian and Hybrid Camels from Dubai

A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice

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