Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial

Abstract

Background Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults. Methods This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter ReedArmy Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18-50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT 02670187) and is completed.Findings Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five [20%] with 0·67 mg, 11 [44%] with 2 mg, and seven [28%] with 6 mg), and malaise or fatigue (five [20%] with 0·67 mg, seven [28%] with 2 mg, and two [8%] with 6 mg). The most common local solicited symptoms were administration site pain (23 [92%] with all three doses) and tenderness (21 [84%] with all three doses). Most solicited symptoms were reported as mild (19 [76%] with 0·67 mg, 20 [80%] with 2 mg, and 17 [68%] with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg grou...

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review

“…Most studies on SARS and MERS vaccines were excluded as they were performed in cell or animal models ( Figure 1). The four studies included in this review were Phase I clinical trials on SARS or MERS vaccines (Table 4) [44][45][46][47]. There were no studies of any population type (cell, animal, human) on the 2019-nCoV at the point of screening.…”

“…The latest findings for these vaccines arebased on the review by Yong et al (2019) in August 2019 [110]. As of the date of reporting, there is only one published clinical study on the MERS-CoV vaccine by GeneOne Life Science & Inovio Pharmaceuticals [47]. There was one SARS vaccine trial conducted by the US National Institute of Allergy and Infectious Diseases.…”

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“…Most of them have been tested in mouse models and showed the ability to elicit neutralizing antibodies. The first SARS-CoV DNA vaccine was tested in humans only 19 months after the virus sequence was published [38], while the DNA vaccine GLS-5300, the first MERS-CoV vaccine, went to clinical trials in 2016 [39]. In addition to these conventional vaccines, Liu et al analyzed the T cell epitopes of SARS-CoV and MERS-CoV, revealed the potential cross-reactivity of the coronaviruses, and assessed the possibility of developing universal vaccines against coronavirus infections [40].…”

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“…Seroconversion was detected in 95% of patients. MERS-CoV-specific T cell responses were detected in 76% of patients and persisted at 60 days post-final immunization [19 ].…”