Immunogenicity consistency and safety with different production scales of recombinant adenovirus type-5 vectored COVID-19 vaccine in healthy adults: a randomized, double-blinded, immunobridging trial.

BACKGROUND: The certification of immunogenicity consistency at different production scales is indispensable for the quality control of vaccines. RESEARCH DESIGN AND METHODS: A randomized, double-blind immunobridging trial in healthy adults aged 18-59 was divided into Scale A (50 L and 800 L) and Scale B (50 L and 500 L) based on vaccine manufacturing scales. Eligible participants in Scale A were randomly assigned to receive the single-dose recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) of different scales at a 1:1 ratio, as was Scale B. The primary endpoint was the geometric mean titer (GMT) of anti-live SARS-CoV-2-specific neutralizing antibodies (NAb) 28 days post-vaccination. RESULTS: 1,012 participants were enrolled, with 253 (25%) per group. The post-vaccination GMTs of NAb were 10.72 (95% CI: 9.43, 12.19) and 13.23 (11.64, 15.03) in Scale A 50 L and 800 L, respectively; 11.64 (10.12, 13.39) and 12.09 (10.48, 13.95) in Scale B 50 L and 500 L, respectively. GMT ratios in Scale A and B have a 95% CI of 0.67-1.5. Most adverse reactions were mild or moderate. 17 of 18 participants reported non-vaccination-related serious adverse reactions. CONCLUSIONS: The Ad5-nCoV in the scale-up production of 500 L and 800 L showed consistent immunogenicity with the original 50 L production scale, respectively.

Immunogenicity and safety of heterologous immunisation with Ad5-nCOV in healthy adults aged 60 years and older primed with an inactivated SARS-CoV-2 vaccine (CoronaVac): a phase 4, randomised, observer-blind, non-inferiority trial.

Background: People over 60 have been found to develop less protection after two doses of inactivated COVID-19 vaccines than younger people. Heterologous immunisation could potentially induce more robust immune responses compared to homologous immunisation. We aimed to assess the immunogenicity and safety of a heterologous immunisation with an adenovirus type 5-vectored vaccine (Ad5-nCOV, Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. Methods: We did a randomised, observer-blinded, non-inferiority trial in healthy adults aged 60 years and older in Lianshui County (Jiangsu, China) between August 26, 2021 and May 15, 2022. 199 eligible participants who had received two doses of CoronaVac in the past 3-6 months were randomised (1:1) to receive a third dose of Convidecia (group A, n = 99) or CoronaVac (group B, n = 100), while 100 participants primed with one dose of CoronaVac in the past 1-2 months were randomised equally to receive a second dose of Convidecia (group C, n = 50) or CoronaVac (group D, n = 50). Participants and investigators were masked to the vaccine received. Primary outcomes were the geometric mean titers (GMTs) of neutralising antibodies against live SARS-CoV-2 virus 14 days after boosting and 28-day adverse reactions. This study was registered with ClinicalTrials.govNCT04952727. Findings: A heterologous third dose of Convidecia resulted in a 6.2-fold (GMTs: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralising antibodies against SARS-CoV-2 wild-type, delta (B.1.617.2) and omicron (BA.1.1) 14 days post boosting, respectively, compared with the homologous boost. The heterologous booster with Convidecia induced significantly higher neutralsing activities, with up to 91% inhibition in binding of Spike to ACE2 for BA.4 and BA.5 variants, compared with 35% inhibition induced by three doses of CoronaVac. For participants primed with one dose of CoronaVac, a heterologous dose of Convidecia induced higher neutralising antibodies against wild-type than two doses of CoronaVac (GMTs: 70.9 vs 9.3, p < 0.0001), but not for that against variants of concern (GMTs against delta: 5.0 vs 4.0, p = 0.4876; GMTs against omicron: 4.8 vs 3.7, p = 0.4707). Adverse reactions were reported by 8 (8.1%) participants in group A and 4 (4.0%) in group B (p ＞ 0.05), and 8 (16.0%) in group C and 1 (2.0%) in group D (p = 0.031). Interpretation: In elderly individuals primed with two doses of CoronaVac, the heterologous immunisation with Convidecia induced strong antibodies against SARS-CoV-2 wildtype and variants of concern, which could be an alternative regimen for enhancing protection in this vulnerable population. Funding: National Natural Science Foundation of China, Jiangsu Provincial Key Research and Development Program, and Jiangsu Science Fund for Distinguished Young Scholars Program.

Environmental Impact Assessment for the Use of an Orally Aerosolized Adenovirus Type-5 Vector-Based COVID-19 Vaccine in Randomized Clinical Trials.

BACKGROUND: An orally aerosolized adenovirus type-5 vector-based coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolized Ad5-nCoV. METHODS: We collected air samples from rooms, swabs from the desks on which the vaccine nebulizer was set, mask samples from participants, and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in serum were detected. RESULTS: Only one (4.00%) air sample collected before initiation of vaccination was positive and most air samples collected during and after vaccination were positive (97.96%, 100%, respectively). All nurses in trial A showed at least 4-fold increase of the neutralizing antibody against SARS-CoV-2 after initiation of the study. In trial B, the proportion of positive mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7. CONCLUSIONS: Vaccination with the orally aerosolized Ad5-nCoV could result in some spillage of the vaccine vector viral particles in the environment and cause human exposure. Clinical Trials Registration. NCT04840992 and NCT05303584.

Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial.

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 × 1011 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 1011 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.

Outbreak of Vaccinia Virus Infection from Occupational Exposure, China, 2017.

Human infections with vaccinia virus (VACV), mostly from laboratory accidents or contact with infected animals, have occurred since smallpox was eradicated in 1980. No recent cases have been reported in China. We report on an outbreak of VACV from occupational exposure to rabbit skins inoculated with VACV.