Phase I-IIA Study of GLS-5300 Vaccine for Mers-Cov: Preliminary Results Demonstrate B and T Cell Immune Response Elicited in Lower-Dose 2-and 3-Vaccination Intradermally Administered Regimens
Authors: Christine C. Roberts, Myoung-don Oh, Eu Suk Kim, Moonsup Jeong, Hyojin Lee, Trina Racine, Emma Reuschel, Celine Remigio, Deborah Kane, Sagar Kudchodkar, Scott White, Young K. Park, David B. Weiner, Joel N. Maslow
Journal: Molecular Therapy (2020)

Background: Novel coronaviruses (CoV) caused 3 global outbreaks over the past 2 decades: SARS-CoV (2002), MERS-CoV (2012), and 2019-nCoV in Wuhan, China. Each caused pneumonia with mortality of 10%, 35% and 2%, respectively (2019-nCoV estimated). GLS-5300 DNA vaccine targeting MERS-CoV Spike (S) was first to enter clinical trial, was safe and immunogenic (Lancet ID;2019). In Phase I, a 3 dose series at Day0, 4 and 12 weeks of GLS-5300 at either 0.67, 2 or 6mg was given IM followed by electroporation (EP, IM+EP) with CELLECTRA-5P device. GLS-5300 induced antibodies (Abs) in 94%, Tcell response in 76%, and neutralizing Abs in 50% of participants. No dose response was observed. GLS-5300 response was similar to those recovered from natural MERS-CoV infection. The absence of dose response and prior experience showing benefits of ID+EP vs IM+EP (JID;2019) led us to design this trial of lower ID dosing with an arm for a 2-dose regimen. We report results from MERS-002, the ongoing Phase I/IIa study of GLS-5300. Methods: MERS-002 is an open label, dose ranging, phase I/IIa study of GLS-5300. Participants were enrolled at 2 Korean sites into 3 groups receiving GLS-5300 ID+EP with the CELLECTRA-3P device: Group 1 received three 0.3mg doses at Day0 and weeks 4 and 12;Group 2 received three 0.6mg doses at Day0 and weeks 4 and 12;Group 3 received two 0.6mg doses at Day0 and week 8. Safety and tolerability of GLS-5300 was evaluated at each visit. Samples were collected at baseline, before each dose, and at both 2 and 4 weeks post dose 2 and post dose 3. Study data through 4 weeks after the primary series for a subset of immunoassays were included here. Findings: GLS-5300 given ID+EP was well-tolerated with no vaccine-associated SAEs. Preliminary results were available for: full length S (flS) ELISA, EMC2012-Vero neutralization (MERS-neut) and MERS-CoV S IFNg ELISPOT. GLS-5300 at 0.6mg induced MERS-CoV-specific Abs by flS ELISA and MERS-neut in 74% and 48%, respectively, after 1 dose. After the 2 or 3 dose vaccine series at 0.6mg per dose, flS ELISA response was seen in 100% and 92% of participants, respectively. MERS-neut response was 92% in both 2 and 3 dose 0.6mg groups. Antibody responses and rates were higher during and after primary series in 0.6mg group regardless of regimen than 0.3mg per dose. GLS-5300 induced Tcell responses via MERS-CoV IFNg ELISPOT in 60% and 84% receiving 0.6mg after the 2 or 3 dose series, respectively. Compared to 0.67mg of GLS-5300 given IM+EP in the first trial, 0.6mg of GLS-5300 given ID+EP in MERS-002, binding Abs appeared sooner and neutralizing Abs were observed in a higher fraction of participants (92% vs 50%) while Tcell reactivity was similar between vaccination schema. Conclusions: GLS-5300 was well tolerated with no vaccine-associated SAEs. Like prior studies, DNA vaccines given by ID+EP had fewer injection-related AEs relative to IM+EP. In MERS-002, 0.6mg of GLS-5300 in a 2-dose regimen spanning 8 weeks had similar reactivity and rate to the longer 3-dose regimen. GLS-5300 was safe and immunogenic when given IM+EP and, similarly, when given ID+EP in both 2- and 3-dose regimens in this ongoing MERS-002 Phase I/IIa trial. A Phase II clinical evaluation of the use of GLS-5300 to prevent MERS-CoV infection in endemic regions is planned.