Safety and immunogenicity of two recombinant DNA COVID-19 vaccines containing the coding regions of the spike or spike and nucleocapsid proteins: an interim analysis of two open-label, non-randomised, phase 1 trials in healthy adults
Abstract:Background
We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein.
Methods
Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled… Show more
“… 8 To our knowledge, in addition to COH04S1 only two other SARS-CoV-2 vaccines co-expressing spike and nucleocapsid are being tested in the clinic. 9 , 10 COH04S1 showed potent immunogenicity in mice, 7 and studies in hamsters and non-human primates showed protection by COH04S1 against upper and lower respiratory tract infection following SARS-CoV-2 challenge. 11 We aimed to assess the safety and immunogenicity of COH04S1 in healthy adults.…”
“… 8 To our knowledge, in addition to COH04S1 only two other SARS-CoV-2 vaccines co-expressing spike and nucleocapsid are being tested in the clinic. 9 , 10 COH04S1 showed potent immunogenicity in mice, 7 and studies in hamsters and non-human primates showed protection by COH04S1 against upper and lower respiratory tract infection following SARS-CoV-2 challenge. 11 We aimed to assess the safety and immunogenicity of COH04S1 in healthy adults.…”
“…An outcome of sterilizing immunity is reducing incidence of viral transmission between the infected and the uninfected, which we successfully demonstrated. The ability to elicit mucosal immune responses and directly dampen transmission even with the Omicron VOC differentiates NanoSTING-NS from IM multi-antigen vaccines 49,50 .…”
Immunization programs against SARS-CoV-2 with commercial intramuscular (IM) vaccines prevent disease but not infections. The continued evolution of variants of concern (VOC) like Delta and Omicron has increased infections even in countries with high vaccination coverage. This is due to commercial vaccines being unable to prevent viral infection in the upper airways and exclusively targeting the spike (S) protein that is subject to continuous evolution facilitating immune escape. Here we report a multi-antigen, intranasal vaccine, NanoSTING-NS that yields sterilizing immunity and leads to the rapid and complete elimination of viral loads in both the lungs and the nostrils upon viral challenge with SARS-CoV-2 VOC. We formulated vaccines with the S and nucleocapsid (N) proteins individually to demonstrate that immune responses against S are sufficient to prevent disease whereas combination immune responses against both proteins prevents viral replication in the nasal compartment. Studies with the highly infectious Omicron VOC showed that even in vaccine-naive animals, a single dose of NanoSTING-NS significantly reduced transmission. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to preventing transmission and ending the pandemic, and (2) an explanation for why hybrid immunity in humans is superior to vaccine-mediated immunity by current IM vaccines.
“…If at least two dilutions of each sample were not included within the standard curve due to low OD value, then the sample was considered as 0.5 BAU/mL. To measure the SARS-CoV-2-specific neutralizing antibody activity induced by the vaccine, a FRNT was performed using Wuhan strain of SARS-CoV-2 using qualified methods as described previously [ 14 ].…”
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.
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