The efficacy, safety and immunogenicity Nanocovax: results of a randomized, double-blind, placebo-controlled Phase 3 trial

Abstract

SummaryBackgroundNanocovax 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.MethodsWe 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.FindingsUp 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.InterpretationNanocovax 25 microgram (mcg) was found to be safe with the efficacy against symptomatic infection of Delta variant of 51.5%.FundingResearch was funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam; ClinicalTrials.gov number, NCT04922788.

Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials

“…Of the 41 053 papers retrieved, 28 eligible efficacy RCTs published in 32 publications were included in this review ( figure 1 ; appendix pp 20–100 ). 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 A total of 286 915 participants in vaccination groups and 233 236 in placebo groups were involved, with a median follow-up ranging from 1 month to 6 months after last vaccination in individual RCTs. 27 eligible RCTs assessed the efficacy of full vaccination for DNA, mRNA, viral vector, inactivated virus, and recombinant protein vaccines.…”

“…27 RCTs investigated vaccine efficacy against symptomatic infection. 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 41 , 43 , 44 , 46 , 47 , 48 , 49 , 50 The combined efficacy was 76·5% (95% CI 69·8–81·7) with high heterogeneity ( I 2 =93·0%, p<0·0001): 67·3% (95% CI 45·8–80·2) for the DNA vaccine, 85·5% (63·5–94·2) for mRNA vaccines, 69·9% (58·2–78·4) for viral vector vaccines, 72·1% (58·9–81·1) for inactivated vaccines, and 76·3% (67·0–82·9) for recombinant protein vaccines ( Figure 2 , Figure 3 ). Vaccine efficacy for preventing symptomatic infection was 78·2% (64·0–86·8) for alpha (B.1.1.7) variants of concern, 33·4% (7·1–52·2) for beta (B.1.351) variants of concern, 73·1% (31·5–89·4) for gamma (P.1) variants of concern, and 67·0% (50·0–78·2) for delta (B.1.617.2) variants of concern.…”

Modular instrumentation for capillary electrophoresis with laser induced fluorescence detection using plug-and-play microfluidic, electrophoretic and optic modules

“…In addition, pressure assistance during electrophoresis, which is not trivial in in-house-made CE instruments, can also applied to accelerate the analysis time or improve the separation resolution, as pressure can be precisely controlled and monitored during application of high voltages (see section below). In in-house made CE instruments [6,9,13,[23][24][25][26][27], a desired pressure value can sometimes not be precisely set and monitored. Thus, optimization of hydrodynamic injection in these cases is generally done with injection time variation rather than pressure adjustment.…”

“…Indeed, such purpose-made instruments are not only much less expensive than commercial systems but can also be constructed as portable versions [2][3][4] or with flexible configurations adapted to different needs [5]. Over 10 years, our groups have demonstrated the use of purpose-made CE devices for various analytical screening applications, notably quality control of antibiotics [6,7], environmental monitoring [8][9][10],…”

“…Exception can be found only for the simplest CE setup with syphoning injection in which an operator only needs a ready-to-use high voltage (HV) module, one capillary and different small vials to carry out electrophoretic separations. Nevertheless, this mode of injection which is the least reproducible, together with manual capillary flushing with a plastic syringe is not fully appreciated by users due to a high risk of contamination during operation and from the air [6].…”