Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine

Abstract

Background Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. Methods Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19–75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). Results Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. Conclusions ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. Trial registration The trial was registered at ClinicalTrials.gov as # NCT04783311.

Engineering Escherichia coli for constitutive production of monophosphoryl lipid A vaccine adjuvant

“…The EuCorVac‐19 vaccine has successfully completed phases I and II of clinical trials (NCT04783311) in Korea. According to the Interim analysis from a phase 2 randomized trial of EuCorVac‐19, EucorVac‐19 was well‐tolerated and induced functional antibodies in a dose‐ and boosting‐specific manner (Lovell et al, 2022). A phase III clinical trial of EuCorVac‐19 is going on in the Philippines (NCT05572879).…”

Human vaccines & immunotherapeutics: News November 2022

“…Two doses of an adjuvanted, nanoliposome-delivered recombinant peptide vaccine, EuCorVac-19 (POP Bio), were safe and induced neutralizing antibodies in 230 healthy adults involved in a dose-escalation, placebo-controlled Phase 2 trial. 1 The vaccine is being tested in two Phase 3 trials.…”

Identification of Enhanced Vaccine Mimotopes for the p15E Murine Cancer Antigen

“…This approach was also used to screen peptide microlibraries for short neoepitopes, leading to the identification of the Nesprin-2 L4492R neoepitope in the Renca cancer cell line, which could be used to inhibit tumor growth ( 16 ). Adjuvanted CoPoP liposomes were recently tested in humans as a COVID-19 vaccine, resulting in the durable induction of neutralizing antibodies without major safety concerns ( 17, 18 ).…”