Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

Alharbi, Naif Khalaf; Qasim, Ibrahim; Almasoud, Abdulrahman; Aljami, Haya A.; Alenazi, Mohamed W.; Alhafufi, Ali; Aldibasi, Omar; Hashem, Anwar M.; Kasem, Samy; Albrahim, Raed; Aldubaib, Musaad; Almansour, Ali; Temperton, Nigel; Kupke, Alexandra; Becker, Stephan; Abu-obaidah, Ali; Alkarar, Ali; Yoon, In-Kyu; Azhar, Esam I.; Lambe, Teresa; Bayoumi, Faisal; Aldowerij, Ali; Ibrahim, Osman H.; Gilbert, Sarah C.; Balkhy, Hanan H.

doi:10.1038/s41598-019-52730-4

Cited by 78 publications

(110 citation statements)

References 47 publications

(50 reference statements)

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“…Although Ad41-S induced humoral immunity in serum, it was significantly less than Ad5-S (39). Chimpanzee adenovirus-based vector systems have also been used (40). In our work, we demonstrated that a single dose as low as 10 4 PFU of PIV5-MERS-S was sufficient to provide 100% protection against lethal MERS-CoV challenge.…”

Section: Discussionmentioning

confidence: 66%

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

Wohlford‐Lenane

et al. 2020

mBio

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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 10 4 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS MA 6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10 6 PFU UV-inactivated MERS MA 6.1.2 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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Section: Discussionmentioning

confidence: 66%

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

Wohlford‐Lenane

et al. 2020

mBio

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“…A good number of these articles were published in high-quality medical and scientific journals and covered both translational and clinical research. Saudi Arabia has started its first ever phase I clinical trial on a vaccine candidate for MERS-CoV (Clinical trial NCT04170829); The MIRACLE trial has started and been ongoing to evaluate antiviral therapeutics in severely infected MERS patients (Clinical trial NCT02845843) and now will include COVID-19 patients, and two vaccines have been developed and tested in animal studies [33,34]; another vaccine has been tested in camels as a one-health veterinary vaccine, since camels are the intermediate host for MERS-CoV [35], in addition to several epidemiologic and observational studies.…”

Section: Mers Emergence and Lesson Learnedmentioning

confidence: 99%

Preparedness and Response to COVID-19 in Saudi Arabia: Lessons Learned from MERS-CoV

Algaissi¹,

Alharbi²,

Hassanain³

et al. 2020

Preprint

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Nearly three months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 550,000 confirmed cases and more than 25,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In the kingdom of Saudi Arabia, unprecedented precautionary strict measures were applied to slow virus entry and to mitigate the risk of the outbreak. Here, we review the experience learned during the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemic in Saudi Arabia, which has been in the country since 2012, and is expected to have helped the country to be well prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.

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“…Following 48 h incubation, cells were lysed and the assay was developed using Bright-Glo™ Luciferase Assay System (Promega, USA) and luciferase activity was measured using a luminometer. 50% of inhibitory concentration (IC50) neutralization titers (in Log10) were calculated for each serum sample using GraphPad Prism (25).…”

Section: Mers Pseudotyped Viral Particles (Merspp) Neutralization Assaymentioning

confidence: 99%

High Rate of Circulating MERS-CoV in Dromedary Camels at Slaughterhouses in Riyadh, 2019

Aljasim

Almasoud

Aljami

et al. 2020

Preprint

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Background: MERS-CoV is a zoonotic virus that have emerged in humans in 2012 and caused severe respiratory illness with mortality rate of 34.4%. Since its appearance, MERS-CoV have been reported in 27 countries and most of these cases were in Saudi Arabia. So far, dromedaries are considered to be the intermediate host and the only known source of human infection. Method: This study was designed to determine the seroprevalence and the infection rate of MERS-CoV in slaughtered food-camels in Riyadh, Saudi Arabia. A total of 171 nasal swabs along with 161 serum samples were collected during the winter; from January to April 2019. Nasal swabs were examined by Rapid test and RT-qPCR to detect MERS-CoV RNA, while serum samples were tested primarily using S1-based ELISA Kit to detect MERS-CoV (IgG) antibodies and subsequently by MERS pseudotyped viral particles (MERSpp) neutralization assay for confirmation. Genetic diversity of the positive isolates was determined based on the amplification and sequencing of the spike gene. Results: Our results showed high prevalence (38%) of MERS-CoV infection in slaughtered camels and high seropositivity (70.81%) during the time of the study. These data indicate previous and ongoing MERS-CoV infection in camels. Phylogenic analysis revealed relatively low genetic variability among our isolated samples. When these isolates were aligned against published spike sequences of MERS-CoV, deposited in global databases, there was sequence similarity of 94%. Conclusion: High seroprevalence and high genetic stability of MERS-CoV in camels indicating that camels pose a public health threat. The widespread of MERS-CoV infections in camels increases the risk of future zoonotic transmission into people with direct contact with these infected camels. This study confirms re-infections in camels, highlighting a challenge for vaccine development when it comes to protective immunity.

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Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

Cited by 78 publications

References 47 publications

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

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

Preparedness and Response to COVID-19 in Saudi Arabia: Lessons Learned from MERS-CoV

High Rate of Circulating MERS-CoV in Dromedary Camels at Slaughterhouses in Riyadh, 2019

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