ABSTRACT
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 × 1011 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 1011 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.
ABSTRACT
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 × 1011 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 1011 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.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Vaccines, InactivatedABSTRACT
Antibody persistence and safety up to 12 months of heterologous orally administered adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in individuals who were primed with two-dose inactivated SARS-CoV-2 vaccine (CoronaVac) previously, has not been reported yet. This randomized, open-label, single-centre trial included Chinese adults who have received two-dose CoronaVac randomized to low-dose or high-dose aerosolised Ad5-nCoV group, or CoronaVac group. In this report, we mainly evaluated the geometric mean titres (GMTs) of neutralizing antibodies (NAbs) against live wild-type SARS-CoV-2 virus and omicron BA.4/5 pseudovirus at 12 months after the booster dose and the incidence of serious adverse events (SAEs) till month 12. Of 419 participants, all were included in the safety analysis and 120 (28.64%) were included in the immunogenicity analysis. Serum NAb GMT against live wild-type SARS-CoV-2 was 204.36 (95% CI 152.91, 273.14) in the low-dose group and 171.38 (95% CI 121.27, 242.19) in the high-dose group at month 12, significantly higher than the GMT in the CoronaVac group (8.00 [95% CI 4.22, 15.17], p < 0.0001). Serum NAb GMT against omicron BA.4/5 pseudovirus was 40.97 (95% CI 30.15, 55.67) in the low-dose group and 35.08 (95% CI 26.31, 46.77) in the high-dose group at month 12, whereas the GMT in the CoronaVac group was below the lower limit of detection. No vaccine-related SAEs were observed. Orally administered aerosolised Ad5-nCoV following two-dose CoronaVac priming has a good safety profile and is persistently more immunogenic than three-dose CoronaVac within 12 months after the booster dose.Trial registration: ClinicalTrials.gov identifier: NCT05043259..
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , SARS-CoV-2ABSTRACT
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 (1·0â×â1011 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0â×â1011 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.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Research , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. METHODS: We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination. RESULTS: One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9), and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination. CONCLUSIONS: Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05313646).
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , COVID-19/prevention & control , Antibodies, Viral , Double-Blind Method , Immunoglobulin G , Adenoviridae , Immunogenicity, VaccineABSTRACT
CoronaVac, also known as the Sinovac inactivated SARS-CoV-2 vaccine, has been widely implemented in combating the COVID-19 pandemic. We summarized the results of clinical trials and real-world studies of CoronaVac in this review. The overall efficacy for the prevention of symptomatic COVID-19 (before the emergence of variants of concern) using two doses of 3 µg CoronaVac was 67.7% (95% CI, 35.9% to 83.7%). Effectiveness in preventing hospitalizations, ICU admissions, and deaths was more prominent than that in preventing COVID-19. A third dose inherited the effectiveness against non-variants of concern and increased effectiveness against severe COVID-19 outcomes caused by omicron variants compared to two doses. Most adverse reactions were mild. Few vaccine-related serious adverse reactions have been reported. Moreover, three-dose regimen significantly increased the seroconversion levels of neutralizing antibodies against omicron as compared to two-dose regimen. This review of CoronaVac may provide a scientific basis for optimizing global immunization strategies.
ABSTRACT
ABSTRACT: A large-scale vaccination of coronavirus disease-19 (COVID-19) in adults has been conducted for nearly a year, and there is a growing recognition that immunization for children is also essential. It has been months since emergency use of pediatric COVID-19 vaccine was approved, we reviewed the prevalence and transmission of COVID-19 in children. The prevalence of COVID-19 in children is reduced due to vaccination even in a Delta prevalent period, so an increase in the vaccination rate is needed in children. Although the precise role of children in the transmission requires more research to uncover, they likely played a significant role, according to the available literature. We also described four candidate COVID-19 vaccines for children on their safety and immunogenicity and the impact of severe acute respiratory syndrome coronavirus 2 variants on childhood vaccination. Safety issues on pediatric vaccines post-approval, like adverse events following immunization and adverse events of special interest require studies on long-term and effective regulatory mechanisms.