Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India

Abstract

Background: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. Methods: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. Findings: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34¢9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36¢36%), 4/12 (33¢33%), 10/10 (100¢00%) and 8/10 (80¢00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. Interpretation: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

Immunogenicity of SARS-CoV-2 trimetric spike protein associated to Poly(I:C) plus Alum

“…This strategy has already been tested for vaccines against other betacoronaviruses such as SARS-CoV (5,6), and MERS-CoV (7). Furthermore, the ID route has also been used for clinical trials of MERS-CoV (NCT03721718) and SARS-CoV-2 vaccines (4,8).…”

Intradermal ChAdOx1 Vaccine Following Two CoronaVac Shots: A Case Report

“…As a viral vector vaccine, ChAdOx1 has been widely used, and several trials have been ongoing, but no evidence on the intradermal administration of viral vector vaccines exists. Only three human studies have demonstrated an excellent humoral and cellular immune response to the intradermal administration of plasmid DNA-ZyCoV-D (Zydus Cadila, Ahmedabad, India) [11], INO-4800 (Inovio Pharmaceuticals, Plymouth Meeting, PA, USA) [12]-and mRNA-1273 (Moderna, Cambridge, MA, USA) [13] vaccines. While the intradermal route was used in the animal models of both the DNA vaccines [14,15], the development of conventional inactivated SARS-CoV-2 or viral vector vaccines has relied only upon intramuscular administration.…”

Nucleic Acid Vaccines for COVID-19: A Paradigm Shift in the Vaccine Development Arena

“…In the study, 0.5 mL of ZyCoV-D vaccine containing 5 mg of DNA plasmid with Spike protein gene region insert suspended in phosphate-buffered saline was administered. The seroconversion rate in volunteers was determined using IgG titers at day 84, and approximately 36.36%, 33.33%, 100% and 80% of subjects were found to be seroconverted in each of the four treatment arms [105].…”