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Background: Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster., Methods: This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 10 11 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 10 11 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing., Findings: Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0-71·4]; p<0·0001)., Interpretation: A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac., Funding: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan., Competing Interests: Declaration of interests J-BG is an employee of CanSino Biologics. Tao Zhu owns stock in CanSino Biologics. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine., Methods: We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 10 11 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 10 11 viral particles per mL; 0·2 mL; high dose group) aerosolised Ad5-nCoV, or a homologous intramuscular vaccination with CoronaVac (0·5 mL). Only laboratory staff were masked to group assignment. The primary endpoint for safety was the incidence of adverse reactions within 14 days after the booster dose. The primary endpoint for immunogenicity was the geometric mean titres (GMTs) of serum neutralising antibodies (NAbs) against live SARS-CoV-2 virus 14 days after the booster dose. This study was registered with ClinicalTrials.gov, NCT05043259., Findings: Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p<0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p<0·0001)., Interpretation: We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination., Funding: National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Carbon dots capped with polyethyleneimine (CD-PEI) were synthesized and applied in selective separation and preconcentration of trace Cr(VI). Dispersed particle extraction (DPE) slurry sampling with flame atomic absorption spectrometry (FAAS) was used to selectively and sensitively determine Cr(VI) in water samples. The as-synthesized CD-PEI was confirmed by Fourier transform infrared spectroscopy, high-resolution transmission electron microscopy, elemental analysis, fluorescence and zeta potential measurement. The adsorption of Cr(VI) on CD-PEI was evaluated. Its isothermal adsorption was studied and fitted in the Langmuir model. Nearly 85% of Cr(VI) was adsorbed within 10 min showed that the CD-PEI exhibited fairly fast kinetics for the sorption of Cr(VI). Experimental conditions, including the content and size of CD-PEI, sample pH, adsorption time, sample volume, slurry volume and interfering ions, were further optimized to obtain efficient preconcentration and high-precision determination of Cr(VI). CD-PEI with small size turned to be a good candidate for the preparation of slurry. CD-PEI served not only as a promising adsorbent for separation and preconcentration of Cr, but also a signal-enhancing agent in FAAS. The method achieved an enhancement factor of 30 and a detection limit (S/N=3) of 0.21 µg L(-1) Cr(VI) with a consumption of 14.0 mL sample and an adsorption time of 5 min, which provided two times of signal enhancement. The RSD for 11 replicate measurements of 5.0 µg L(-1) Cr(VI) was 2.8%. The possible signal enhancement mechanism was proposed. The developed method has been applied to determine trace Cr(VI) in a variety of water samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Interest in carbon nanotubes for detecting the presence of pathogens arises because of developments in chemical vapor deposition synthesis and progresses in biomolecular modification. Here we reported the facile synthesis of multi-walled carbon nanotubes (MWCNTs), which functioned as immuno-, magnetic, fluorescent sensors in detecting Vibrio alginolyticus (Va). The structures and properties of functionalized MWCNTs were characterized by ultraviolet (UV), Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), magnetic property measurement system (MPMS) and fluorescent spectra (FL). It was found that the functionalized MWCNTs showed: (1) low nonspecific adsorption for antibody-antigen, (2) strong interaction with antibody, and (3) high immune-magnetic activity for pathogenic cells. Further investigations revealed a strong positive linear relationship (R=0.9912) between the fluorescence intensity and the concentration of Va in the range of 9.0 × 10(2) to 1.5 × 10(6) cfum L(-1). Moreover, the relative standard deviation for 11 replicate detections of 1.0 × 10(4) cfum L(-1) Va was 2.4%, and no cross-reaction with the other four strains was found, indicating a good specificity for Va detection. These results demonstrated the remarkable advantages of the multifunctional MWCNTs, which offer great potential for the rapid, sensitive and quantitative detection of Va in fishery and environmental samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine., Methods: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247., Findings: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33)., Interpretation: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity., Funding: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children., Methods: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6–36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853., Findings: We randomly assigned 1200 participants, 240 (120 aged 6–11 months [infants] and 120 aged 12–36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3–954·3]), followed by those who received the 320 U formulation (497·9 [383·1–647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3–1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9–676·6] in infants and 708·4 [524·1–957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5–457·5] in infants and 498·0 [383·4–646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9–48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001)., Interpretation: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials., Funding: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12–5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.