A randomized phase I/II safety and immunogenicity study of the Montanide-adjuvanted SARS-CoV-2 spike protein-RBD-Fc vaccine,AKS-452

BackgroundPrevious interim data from a phase I study of AKS-452, a subunit vaccine comprising an Fc fusion of the respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (SP/RBD) emulsified in the water-in-oil adjuvant, Montanide™ ISA 720, suggested a good safety and immunogenicity profile in healthy adults. This phase I study was completed and two dosing regimens were further evaluated in this phase II study.MethodsThis phase II randomized, open-labelled, parallel group study was conducted at a single site in The Netherlands with 52 healthy adults (18 – 72 years) receiving AKS-452 subcutaneously at one 90 µg dose (cohort 1, 26 subjects) or two 45 µg doses 28 days apart (cohort 2, 26 subjects). Serum samples were collected at the first dose (day 0) and at days 28, 56, 90, and 180. Safety and immunogenicity endpoints were assessed, along with induction of IgG isotypes, cross-reactive immunity against viral variants, and IFN-γ T cell responses.ResultsAll AEs were mild/moderate (grades 1 or 2), and no SAEs were attributable to AKS-452. Seroconversion rates reached 100% in both cohorts, although cohort 2 showed greater geometric mean IgG titers that were stable through day 180 and associated with enhanced potencies of SP/RBD-ACE2 binding inhibition and live virus neutralization. AKS-452-induced IgG titers strongly bound mutant SP/RBD from several SARS-CoV-2 variants (including Omicrons) that were predominantly of the favorable IgG1/3 isotype and IFN-γ-producing T cell phenotype.ConclusionThese favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.     

Immunogenicity and safety of a single booster dose of NVX-CoV2373 (TAK-019) in healthy Japanese adults who had previously received a primary series of COVID-19 mRNA vaccine: Primary analysis report of a phase 3 open-label trial

BackgroundWe evaluated the immunogenicity and safety of a booster dose of NVX-CoV2373 in Japanese adults who had completed a primary series of COVID-19 mRNA vaccine 6–12 months previously.MethodsThis single-arm, open-label, phase 3 study, conducted at two Japanese centres, enrolled healthy adults ≥ 20 years old. Participants received a booster dose of NVX-CoV2373. The primary immunogenicity endpoint was non-inferiority (lower limit of the 95 % confidence interval [CI] ≥ 0.67) of the geometric mean titre (GMT) ratio of titres of serum neutralizing antibodies (nAbs) against the SARS-CoV-2 ancestral strain 14 days after booster vaccination (day 15) in this study, compared with those 14 days after the second primary NVX-CoV2373 vaccination (day 36) in the TAK-019-1501 study (NCT04712110). Primary safety endpoints included local and systemic solicited adverse events (AEs) up to day 7 and unsolicited AEs up to day 28.ResultsBetween 15 April 2022 and 10 May 2022, 155 participants were screened and 150, stratified by age (20–64 years old [n = 135] or ≥ 65 years old [n = 15]), received an NVX-CoV2373 booster dose. The GMT ratio between titres of serum nAbs against the SARS-CoV-2 ancestral strain on day 15 in this study and those on day 36 in the TAK-019-1501 study was 1.18 (95 % CI, 0.95–1.47), meeting the non-inferiority criterion. Following vaccination, the proportion of participants who reported local and systemic solicited AEs up to day 7 was 74.0 % and 48.0 %, respectively. The most common local and systemic solicited AEs were tenderness (102 participants [68.0 %]) and malaise (39 participants [26.0 %]), respectively. Seven participants (4.7 %) reported unsolicited AEs between vaccination and day 28; all were severity grade ≤ 2.DiscussionA single heterologous NVX-CoV2373 booster induced rapid and robust anti-SARS-CoV-2 immune responses, addressing waning immunity in healthy Japanese adults, and had an acceptable safety profile.ClinicalTrials.gov identifier: NCT05299359.     

青蒿素和槲皮素抑制新冠病毒刺突蛋白介导的细胞因子风暴

目的 研究青蒿素和槲皮素的单独或联合治疗是否能改善新冠病毒(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)的棘突蛋白(spike protein, S蛋白)介导的细胞因子风暴。方法 进行细胞活力测定,而后检测青蒿素或槲皮素单独或联合处理对SARS-CoV-2的S蛋白介导的细胞因子风暴的改善作用。结果 在SARS-CoV-2 S蛋白刺激下，青蒿素或槲皮素的单独或联合治疗可以通过抑制NFKB的过度激活来显著减轻细胞因子风暴。结论 单独和联合使用青蒿素和槲皮素均能有效地抑制SARS-CoV-2 S蛋白介导的细胞因子风暴。     

Comparison of nucleocapsid and spike antibody ELISAs for determining SARS-CoV-2 seropositivity in Kenyan women and infants

A multitude of enzyme-linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies since the coronavirus disease 2019 pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio-Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother–infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R² = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS-CoV-2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS-CoV-2 Total Ab ELISA as a suitable high-throughput method for seroprevalence studies in Kenya.     

Applying the Inelastic Thermal Spike Model to the Investigation of Damage Induced by High-Energy Ions in Polymers

This work reports on damage production in polymers by high-energy ions within the framework of the inelastic thermal spike model (i-TS). The model is used to describe the effective size of the damaged region around the ion path (the track size) in amorphous poly(methyl methacrylate) (PMMA) and the semicrystalline poly(p-phenylene sulphide) (PPS), poly(ethylene terephthalate) (PET), and poly(vinylidene difluoride) (PVDF). Track size calculations are compared to experimental data deduced from measurements of crater size, bond-breaking cross-sections, changes in crystallinity and electron density, track etching, and electrical depolarization. The use of data obtained from distinct types of damage provides a broad platform to test the applicability of the model to polymers. This work shows that the i-TS correctly describes the dependence of the track size on energy loss obtained from most experimental probes, when the activation energy of thermal decomposition of the polymers is used as the criterion of track formation, using an electron–phonon mean free path of ≈3 nm. As damage is not uniform across the ion track radial dimension, there are fine variations in the experimental damage radii that can only be accounted for by using multiple activation processes. Amorphization radii of the semicrystalline polymers are not directly correlated to melting induced by the ions.