ABSTRACT
Background: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018.Methods: 45 healthy adults from 20 to 49 years of age were to be administered two vaccinations of MVC-COV1901 in doses of 5 μg, 15 μg, or 25 μg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second vaccination at the time of the interim analysis. Adverse events (AEs) and laboratory data were recorded for the safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays, SARS-CoV-2 spike-specific immunoglobulin G (IgG), and cellular immune response at various time points.Findings: Solicited adverse events were mostly mild and similar in all three dose groups. No subject experienced fever. After the second vaccination, serum neutralizing activity for wild-type virus was detected in all participants of the 15 μg and 25 μg dose groups with geometric mean values (76•3 [95% CI: 53•75 ~108•33], and 167•4 [95% CI: 122.05 ~229.61]) 1•8 to 3•9 times those of a panel of control convalescent serum specimens (42•7, [95%CI: 26•38~69•04]). The cellular immune response induced by MVC-COV1901 demonstrated substantially higher numbers of IFN-γ- than IL-4- producing cells in human peripheral blood mononuclear cells, suggesting a Th1-skewed immune response.Interpretation: The MVC-COV1901 vaccine was well tolerated and elicited robust immune responses especially in the 15 μg and 25 μg dose groups and is suitable for further development.Trial Registration: ClinicalTrials.gov NCT 04487210Funding: Medigen Vaccine Biologics Corporation.Conflict of Interest: Szu-Min Hsieh, Shan-Chwen Chang, Wang-Da Liu, Yu-Shan Huang declared that they have no knowncompeting financial interests or personal relationships that could have appeared to influence the work reported in this paper; Yi-Jiun Lin, Erh-Fang Hsieh, Wei-Cheng Lian, Charles Chen, I-Chen Tai are employee ofMedigen Vaccine Biologics Corporation and reported grants from Taiwan Centers for Disease Control, Ministry of Health and Welfare, during the conduct of the study. In addition, Yi-Jiun. Lin and Charles Chen have a patent US63/040,696 pending. Robert Janssen is an employee of Dynavax Technologies Corporation.Ethical Approval: The trial protocol and informed consent form were approved by the Taiwan Food and Drug Administration and the ethics committee at the site. The trial was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. An independent data and safety monitoring board (DSMB) was established to monitor safety data and the trial conduct.
Subject(s)
FeverABSTRACT
Design This is a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a recombinant stabilized prefusion SARS-CoV-2 spike (S-2P) protein vaccine with adjuvant of aluminum hydroxide and CpG 1018. Methods We enrolled 45 healthy adults from 20 to 49 years of age to be administered with two vaccinations of MVC-COV1901 in a low dose (LD), middle dose (MD), and high dose (HD) of spike protein at 28 days apart. There were 15 participants in each dose group, and all of them were followed up for 28 days after the second vaccination at the time of interim analysis. Adverse events (AEs) and laboratory data were recorded for safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays as well as SARS-CoV-2 spike-specific immunoglobulin G (IgG) at various times. Overall, the study duration will be 7 months. Results Solicited events were mostly mild and similar in the participants of all three dose groups. No subject experienced fever. There were no serious nor adverse events of special interest at the time point of this interim report. After the second vaccination, the SARS-CoV-2 spike specific IgG titers increased with peak geometric mean titers at 7178.245 (LD), 7746.086 (MD), and 11220.58 (HD), respectively. Serum neutralizing activity was detected by two methods in all participants of MD and HD groups, with geometric mean values generally comparable to those of a panel of control convalescent serum specimens. All of the participants in the MD and HD groups were seroconverted after the second vaccination. Conclusions The MVC-COV1901 vaccine is safe and elicits remarkable immune responses especially in the MD and HD groups.
Subject(s)
Fever , Severe Acute Respiratory Syndrome , Infarction, Middle Cerebral ArteryABSTRACT
Background: The Coronavirus -19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) is an ongoing world-wide plague. The viral spike (S) coat protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for COVID-19 in patients taking angiotensin-converting enzyme inhibitors (ACEI)/ angiotensin II type 1 receptor antagonists (ARBs). Methods: We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization data-base of COVID-19 publications and ClinicalTrials.gov through Jun 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study has been registered with PROSPERO, CRD42020190666. Findings: 14,921 ACEi users and 149,163 non-users were included. In the eligible studies, 2,756 ACEi users tested positive among a total of 22,114 patients of SARS-CoV-2 infection. 22,685 ARBs users and 141,399 non-users were included. In the eligible studies, 3,352 ARBs users tested positive among 22,114 patients of SARS-CoV-2 infection. After pooling the adjusted odds ratios (aOR), no significant increase was noted in the risk of SARS-CoV-2 infection by ACEi (aOR, 0.95; 95% CI, 0.86-1.05) or ARBs (aOR, 1.05; 95% CI, 0.97-1.14) users. However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with ARBs usage (coefficient, -0.006; 95% CI, -0.016 to 0.004)-i.e.: the use of ARBs, as opposed to ACEi, specifically augmented the risk of SARS-CoV-2 infection in subjects < 60 years-old. In the COVID-19 outcome analysis, neither ACEi (aOR, 1.00; 95% CI, 0.80-1.26) nor ARBs (aOR, 0.99; 95% CI, 0.83-1.18) usage aggravated disease severity or mortality of COVID-19. Interpretation: ACEi usage might not increase the susceptibility of SARS-CoV-2 infection, severity of disease and mortality in case-population and cohort studies. Additionally, we found for the first time that the usage of ARBs, as opposed to ACEi, specifically augmented the risk of SARS-CoV-2 infection in younger subjects; without obvious effects on COVID-19 outcomes.Funding Statement: This study was supported by Taiwan National Science Council (grants NSC 101- 2314-B-002-132-MY3, NSC100-2314-B-002-119, NSC 101-2314-B-002-085-MY3, MOST 104-2314-B-002 -125 -MY3) and NTUH 100-N1776, 101-M1953, 102- S2097. Declaration of Interests: The authors declare that they have no competing interest.