ABSTRACT
Background Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. In a Phase 1 and 2 studies, (NCT04683484) the vaccine was found to be safe and induce a robust immune response in healthy adult participants. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, immunogenicity, and protective efficacy of the Nanocovax vaccine against Covid-19 in approximately 13,007 volunteers aged 18 years and over. The immunogenicity was assessed based on Anti-S IgG antibody response, surrogate virus neutralization, wild-type SARS-CoV-2 neutralization and the types of helper T-cell response by intracellular staining (ICS) for interferon gamma (IFNg) and interleukin-4 (IL-4). The vaccine efficacy (VE) was calculated basing on serologically confirmed cases of Covid-19. Findings Up to day 180, incidences of solicited and unsolicited adverse events (AE) were similar between vaccine and placebo groups. 100 serious adverse events (SAE) were observed in both vaccine and placebo groups (out of total 13007 participants). 96 out of these 100 SAEs were determined to be unrelated to the investigational products. 4 SAEs were possibly related, as determined by the Data and Safety Monitoring Board (DSMB) and investigators. Reactogenicity was absent or mild in the majority of participants and of short duration. These findings highlight the excellent safety profile of Nanocovax. Regarding immunogenicity, Nanocovax induced robust IgG and neutralizing antibody responses. Importantly, Anti S-IgG levels and neutralizing antibody titers on day 42 were higher than those of natural infected cases. Nanocovax was found to induce Th2 polarization rather than Th1. Post-hoc analysis showed that the VE against symptomatic disease was 51.5% (95% confidence interval [CI] was [34.4%-64.1%]. VE against severe illness and death were 93.3% [62.2- 98.1]. Notably, the dominant strain during the period of this study was Delta variant. Interpretation Nanocovax 25 microgram (mcg) was found to be safe with the efficacy against symptomatic infection of Delta variant of 51.5%.
Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Respiratory InsufficiencyABSTRACT
Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant.Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 microgram (mcg), 50 mcg, and 75 mcg doses, aluminum hydroxide adjuvanted). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2 which involved in 560 healthy adults, the primary outcomes are vaccine safety, and anti-S IgG antibody response. Secondary outcomes were surrogate virus neutralization, wild-type SARS-CoV-2 neutralization, and T-cell responses by intracellular staining (ICS) for interferon gamma (IFNg). Anti-S IgG and neutralizing antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients.Findings: For phase 1 study, no serious adverse events (SAE) were observed for all 60 participants. Most adverse events (AE) were grade 1 and disappeared shortly after injection. For phase 2 study, after randomization, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive placebo. Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups up to day 90. Anti S-IgG levels and neutralizing antibody titers at the peak response on day 42 were all higher than those of convalescent sera.Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. 25 mcg was selected for a phase 3 trial to evaluate the vaccine efficacy.Trial Registration: ClinicalTrials.gov number, NCT04683484. NCT04683484, registration date in clinicaltrial.gov is Dec24, 2020, We has started our Phase 1 clinical trial in Vietnam on Dec 17, 2020,Funding: Research funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of VietnamDeclaration of Interest: The following authors Thuy Phuong Nguyen, Hiep Khong, Tri Minh Le, Tuyen Thi Ngoc Trang, Thanh Thi Dinh, Thuong Van Vo, Thao Thi Thu Vu, Quynh Bao Phuong Nguyen, Vuong Tan Phan, Vinh The Tran, Mai Thi Nhu Tran, Truc Thi Thanh Nguyen, Phat Tan Ha, Hieu Trong Huynh, Khanh Duy Nguyen, Chung Chinh Doan, Thuan Trong Ung, Si Minh Do are employees of Nanogen Pharmaceutical Biotechnology JSC. All other authors declare no competing interests.Ethical Approval: The trials were designed and funded by Nanogen Pharmaceutical Biotechnology JSC and the Ministry of Science and Technology (MOST) of Vietnam. The trial protocol was approved by the Ethics Committee/Protocol Review Board of the Ministry of Health (Vietnam)
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
BackgroundThere is a shortage of chemical reagents for severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) diagnosis and a surge of SARS-CoV-2cases, especially in limited-resource settings. Therefore, the combination of an optimal assay kit is necessary. MethodsWe compared the ability to screen SARS-CoV-2 among three primer-probe sets in two different master mixes, Invitrogen SuperScript III One-Step RT-PCR and LightCycler Multiplex RNA Virus Master. ResultsThe assay with TIB-Molbiol, IDT, and Phu Sa sets for LightCycler Multiplex RNA Virus Master or Invitrogen SuperScript III One-Step RT-PCR showed positive results from a single reaction of triplicate in the three days of 4.8 copies per reaction. R-squared and amplification efficiency were 0.97 and ranged from 107 to 108%, respectively. ConclusionsOur findings indicated that TIB-Molbiol, IDT, and Phu Sa primer-probe sets could be beneficial for the laboratory screening of SARS-CoV-2 by RT-qPCR assay of E gene. There is a need to consider the combination of these reagent sets as a new strategy to increase the testing capacity of screening programs for COVID-19.
Subject(s)
COVID-19ABSTRACT
The pandemic COVID-19 caused by the zoonotic virus SARS-CoV-2 has devastated countries worldwide, infecting more than 4.5 million people and leading to more than 300,000 deaths. Whole genome sequencing (WGS) is an effective tool to monitor emerging strains and provide information for intervention, thus help to inform outbreak control decisions. Here, we reported the first effort to sequence and de novo assemble the whole genome of SARS-CoV-2 using PacBios SMRT sequencing technology in Vietnam. We also presented the annotation results and a brief analysis of the variants found in our SARS-CoV-2 strain, which was isolated from a Vietnamese patient. The sequencing was successfully completed and de novo assembled in less than 30 hours, resulting in one contig with no gap and a length of 29,766 bp. All detected variants as compared to the NCBI reference were highly accurate as confirmed by Sanger sequencing. The results have shown the potential of long read sequencing to provide high quality WGS data to support public health responses, and advance understanding of this and future pandemics.