Safety and immunogenicity of ChAdOx1 MERS vaccine candidate in healthy Middle Eastern adults (MERS002): an open-label, non-randomised, dose-escalation, phase 1b trial

Bosaeed, Mohammad; Balkhy, Hanan H.; Almaziad, Sultan; Aljami, Haya A.; Alhatmi, Hind; Alanazi, Hala; Alahmadi, Mashael; Jawhary, Ayah; Alenazi, Mohammed W.; Almasoud, Abdulrahman; Alanazi, Rawan; Bittaye, Mustapha; Aboagye, Jeremy; Albaalharith, Nahla; Batawi, Sarah; Folegatti, Pedro M.; Lopez, Fernando Ramos; Ewer, Katie; Almoaikel, Khalid; Al-Jeraisy, Majed; Alothman, Adel; Gilbert, Sarah C.; Alharbi, Naif Khalaf

doi:10.1016/s2666-5247(21)00193-2

Cited by 37 publications

(35 citation statements)

References 35 publications

(64 reference statements)

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“…This demonstrates the importance of carrying out in vivo histopathological analysis in appropriate models when studying VAED. This vaccine has been assessed in phase 1 trials with promising safety and immunogenicity data ( 103 ) but any concerns of VAED can only be monitored if larger trials are conducted where vaccinees are exposed to MERS-CoV infection. Safe and effective vaccination against MERS virus using a modified vaccinia Ankara (MVA) viral vector has also been observed in mice ( 104 , 105 ) and in dromedary camels, the reservoir host of the virus ( 106 ).…”

Section: Vaccine-associated Enhanced Disease In Pathogenic Coronavirusesmentioning

confidence: 99%

Vaccine-Associated Enhanced Disease and Pathogenic Human Coronaviruses

Gartlan

Tipton

Salguero³

et al. 2022

Front. Immunol.

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Vaccine-associated enhanced disease (VAED) is a difficult phenomenon to define and can be confused with vaccine failure. Using studies on respiratory syncytial virus (RSV) vaccination and dengue virus infection, we highlight known and theoretical mechanisms of VAED, including antibody-dependent enhancement (ADE), antibody-enhanced disease (AED) and Th2-mediated pathology. We also critically review the literature surrounding this phenomenon in pathogenic human coronaviruses, including MERS-CoV, SARS-CoV-1 and SARS-CoV-2. Poor quality histopathological data and a lack of consistency in defining severe pathology and VAED in preclinical studies of MERS-CoV and SARS-CoV-1 vaccines in particular make it difficult to interrogate potential cases of VAED. Fortuitously, there have been only few reports of mild VAED in SARS-CoV-2 vaccination in preclinical models and no observations in their clinical use. We describe the problem areas and discuss methods to improve the characterisation of VAED in the future.

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Section: Vaccine-associated Enhanced Disease In Pathogenic Coronavirusesmentioning

confidence: 99%

Vaccine-Associated Enhanced Disease and Pathogenic Human Coronaviruses

Gartlan

Tipton

Salguero³

et al. 2022

Front. Immunol.

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“…Therefore, it is critical to have vaccines against multiple coronavirus species, ideally as pan-coronavirus vaccines, to help fight not only the current pandemic, but also to prevent the re-emergence of the previously existed pathogenic species, as well as constantly evolving and lurking coronavirus diseases as probable future outbreaks. Various prior efforts led to the development of SARS and MERS vaccine candidates, although at earlier stages of development [11][12][13][14][15] . The COVID-19 pandemic urged an international effort for rapid development of vaccines against SARS-CoV-2 16 , leading to multiple successful candidates including the highly efficacious mRNA vaccines 17,18 .…”

Section: Discussionmentioning

confidence: 99%

“…Before the COVID-19 pandemic, no effective vaccine had been approved to prevent spread of coronaviruses. Previous SARS and MERS vaccine devolvement [11][12][13][14][15] , although at earlier stages, together with global efforts, led to rapid development of multiple COVID-19 vaccines against SARS-CoV-2 16 . The most prominent and efficacious vaccine belong to the lipid nanoparticle (LNP) mRNA vaccine category, with the first two emergency use approval issued to Moderna and Pfizer-BioNTech mRNA vaccines 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Simultaneous and sequential multi-species coronavirus vaccination

Peng

Fang

Renauer

et al. 2022

Preprint

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Although successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.One sentence summaryMultiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.

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“…Following demonstration that a single dose of a ChAdOx1 MERS-CoV vaccine generated protective immunity in non-human primates (NHP), the candidate completed Phase 1 human trials, where it proved to be well tolerated, and elicited humoral and cellular responses [ 61 , 90 ]. These data informed the selection of this platform for the development of AZD1222 to target SARS-CoV-2.…”

Section: Virus Vectors In Developmentmentioning

confidence: 99%

Utilization of Viral Vector Vaccines in Preparing for Future Pandemics

2022

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As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics.

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Safety and immunogenicity of ChAdOx1 MERS vaccine candidate in healthy Middle Eastern adults (MERS002): an open-label, non-randomised, dose-escalation, phase 1b trial

Cited by 37 publications

References 35 publications

Vaccine-Associated Enhanced Disease and Pathogenic Human Coronaviruses

Vaccine-Associated Enhanced Disease and Pathogenic Human Coronaviruses

Simultaneous and sequential multi-species coronavirus vaccination

Utilization of Viral Vector Vaccines in Preparing for Future Pandemics

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