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1.
Clin Infect Dis ; 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-2017764

ABSTRACT

BACKGROUND: We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine with homologous prime-boost regimens in healthy participants aged 6 years and above. METHODS: In this randomised, double-blind, placebo-controlled trial, participants received low-dose vaccine, middle-dose vaccine or placebo. Prime-booster regimens were given intramuscularly 56 days apart. ELISA antibodies to the receptor binding domain (RBD) and pseudovirus neutralising antibodies were detected. Adverse events were monitored for 28 days following each vaccination. RESULTS: A total of 430 participants were enrolled in the study, with 30 participants aged 18-55 years (MID cohort), 250 participants aged 56 years and older (OLD cohort), and 150 participants aged 6-17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies which decreased with increasing age, with geometric mean titres (GMTs) of 1037.5 in MIN cohort, 647.2 in MID cohort, and 338.0 in OLD cohort receiving 5×10 10 viral particles on day 28 following boost vaccination. Pseudovirus neutralising antibodies showed a similar pattern, with GMTs of 168.0 in MIN cohort, 76.8 in MID cohort, and 79.7 in OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by two doses in adults, with GMTs of 1091.6 and 96.6 in ELISA antibody and neutralising antibody, respectively. Homologous prime-boost vaccination was safety and tolerable. CONCLUSIONS: Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6-17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine.

3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(8): 1127-1135, 2022 Aug 06.
Article in Chinese | MEDLINE | ID: covidwho-1974960

ABSTRACT

The COVID-19 outbreak at the end of 2019 has accelerated the development and research for COVID-19 vaccines worldwide. Among the COVID-19 vaccines in clinical trials developed via different platforms, recombinant virus vector-based vaccines have shown excellent immunogenicity and efficacy. However, at the same time, there are serious issues such as vaccine safety and pre-existing antibodies against vectors. This article summarizes the design concept and development history of recombinant virus vector-based vaccines, and focuses on the progress in the clinical studies of vector-based COVID-19 vaccines as well as the challenges, in order to provide reference for the research of recombinant vector-based vaccines.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Genetic Vectors , Humans , Vaccines, Synthetic
4.
Hum Vaccin Immunother ; : 2096970, 2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1956540

ABSTRACT

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.

5.
Diabetes Metab Syndr Obes ; 15: 1413-1422, 2022.
Article in English | MEDLINE | ID: covidwho-1951752

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) outbreak has seriously affected people's lives, especially those with chronic diseases. Diabetes self-management, which plays an important role in glycaemic control and reducing the risk of acute and long-term complications, may be discouraged by social distancing. Purpose: To evaluate the level of self-management activities in Chinese patients with type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic. Patients and Methods: A survey of with 872 patients with T2DM in the inpatient and outpatient departments through face-to-face interviews was conducted from 1 July, 2020 to 30 September, 2020. The main outcome measures were glycaemic control status and level of self-management activities during the pandemic. Results: In terms of glycaemic control, the data showed that patients with fasting plasma glucose (FPG) < 7.0 mmol/L (36.4%), postprandial plasma glucose (PPG) < 10.0 mmol/L (26.3%), or glycosylated haemoglobin (HbA1c) < 7.0% (18.6%) in our investigation has well-controlled blood glucose level, and 11.9% of patients experienced blood glucose <3.9 mmol/L during the outbreak. The diabetes self-management of Chinese patients decreased and the final diabetes self-management score of the Chinese patients was 3.4 ± 1.45. Patients with higher education, diabetes education, comorbidities, and online consultations had higher diabetes self-management scores (P <0.05). Adherence to diabetes self-management in the normal glycaemic control group was higher than that in the substandard glycaemic control group (P<0.05). Among all participants, 72.1% of the patients reduced the frequency of hospital visits, and 44.8% considered that they had diabetes-related stress during the pandemic. The mean anxiety level score rated by 286 patients was 5.3±2.8. Conclusion: The COVID-19 pandemic has affected diabetes self-management, including substandard glycemic control, increased diabetes-related stress, limited exercise range and medical visits. Therefore, future interventions should focus on the online management of chronic diseases and support online consultation' development and promotion, which can overcome physical distance and provide personalized services conveniently.

6.
Chin Med J (Engl) ; 2022 Jul 14.
Article in English | MEDLINE | ID: covidwho-1931923

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 long-term and effective regulatory mechanisms to make sure.

8.
Adv Ther ; 39(8): 3789-3798, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1906546

ABSTRACT

INTRODUCTION: BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified mRNA SARS-CoV-2 vaccine. Here, we report safety and immune persistence data following a primary two-dose vaccination schedule administered 21 days apart. METHODS: Immune persistence was determined at month 3 in 72 younger participants (aged 18-55 years) and at month 6 in 70 younger and 69 older participants (aged 65-85 years). RESULTS: In younger participants, neutralizing antibody (nAb) geometric mean titers (GMTs) for the 10 and 30 µg dose levels declined from 233 and 254 (21 days after dose 2) to 55 and 87 at month 3, respectively, and to 16 and 27 at month 6, respectively. In older participants, nAb GMTs declined from 80 and 160 (21 days after dose 2) to 10 and 21 at month 6. Overall, higher antibody titers were observed in younger participants, and the 30 µg dose induced higher levels of nAb, which declined more slowly by month 6. No serious adverse events were reported in the vaccine group. CONCLUSION: This study showed BNT162b1 maintains a favorable safety profile in younger and older participants in the 6 months after vaccination. This study further extends our understanding of immune persistence and the safety of the BNT162b1 vaccine as a candidate vaccine in the BioNTech pipeline. TRIAL REGISTRATION NUMBER: NCT04523571, registered August 21, 2020.


Subject(s)
BNT162 Vaccine , COVID-19 , Vaccines , Adult , Aged , Antibodies, Neutralizing , BNT162 Vaccine/adverse effects , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , China , Double-Blind Method , Humans , Liposomes , Nanoparticles , RNA, Messenger , SARS-CoV-2 , Vaccination
9.
Lancet Respir Med ; 10(8): 749-760, 2022 08.
Article in English | MEDLINE | ID: covidwho-1867947

ABSTRACT

BACKGROUND: All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults. METHODS: We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0-44; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-γ ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. χ2 test and Fisher's exact test were used to analyse categorical data, and t test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316). FINDINGS: Between Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42-51]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31-49]) of 120 vaccine recipients compared with one (1% [0-5]) of 111 placebo recipients (p<0·0001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8-13]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3·8 [95% CI 3·4-4·3] in responders), and in 31 (22% [15-29]) of 143 vaccine recipients (GMT 4·4 [3·3-5·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. 57 (12% [95% CI 9-16]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3·8 [95% CI 3·5-4·1] in responders) in the phase 2 trial, as did 18 (13% [8-19]) of 143 vaccine recipients (GMT 5·2 [4·0-6·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. INTERPRETATION: dNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration. FUNDING: National Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.


Subject(s)
COVID-19 Vaccines , COVID-19 , Orthomyxoviridae , Viral Vaccines , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Humans , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Vaccines, Attenuated/adverse effects
10.
PLoS Med ; 19(5): e1003953, 2022 05.
Article in English | MEDLINE | ID: covidwho-1865330

ABSTRACT

BACKGROUND: Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). METHODS AND FINDINGS: We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data. CONCLUSIONS: Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines. TRIAL REGISTRATION: Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101.


Subject(s)
COVID-19 , Influenza Vaccines , Adenoviridae/genetics , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Humans , Immunogenicity, Vaccine , SARS-CoV-2 , Vaccination , Vaccines, Synthetic/adverse effects
11.
Lancet Respir Med ; 10(8): 739-748, 2022 08.
Article in English | MEDLINE | ID: covidwho-1852285

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Research , SARS-CoV-2 , Vaccination
12.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336899

ABSTRACT

Summary Background The ReCOV is a recombinant trimeric two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03. We report the preliminary safety and immunogenicity results for the ReCOV. Methods This first in human, randomized, double-blind, placebo-controlled phase I study, was conducted at 2 study sites in New Zealand. Subjects were stratified into two age cohorts (18-55 years and 56-80 years old) and then randomly assigned in a 4:1 ratio to receive two 0.5 mL intramuscular doses of the ReCOV vaccine (20µg or 40µg, adjuvanted with BFA03 in each) or placebo, 21 days apart. The primary endpoints were incidence of solicited local and systemic adverse events (AEs) and unsolicited AEs after each dose;incidence of serious adverse events (SAEs) up to 30 days after the second dose;changes in clinical laboratory tests from baseline up to 7 days after each dose;and changes in vital signs from baseline up to 30 days after the second dose. The key secondary endpoints for immunogenicity were neutralizing antibody titers against SARS-CoV-2, S1 receptor binding domain (RBD) and N-terminal domain (NTD) IgG titers post-vaccination. The T cell-specific immune response elicited by ReCOV were also evaluated. The trial was registered with ClinicalTrials.gov ( NCT04818801 ). Findings One hundred participants (50 for each age group) were randomized. The incidence of solicited local AEs in 20μg ReCOV, 40μg ReCOV, and pooled placebo group among younger adults were 60.0%, 70.0%, and 10.0%, respectively, while among older adults were 55.0%, 84.2%, and 10.0%, respectively. The incidence of solicited systemic AEs in 20μg ReCOV, 40μg ReCOV, and pooled placebo group among younger adults were 60.0%, 60.0%, and 30.0%, respectively, while among older adults were 50.0%, 52.6%, and 50.0%, respectively. All solicited AEs and unsolicited AEs were mild. No vaccination-related SAE, adverse events of special interest, and AE leading to early discontinuation were reported. ReCOV elicited SARS-CoV-2 neutralizing antibody after the first vaccination, which were increased further after the second vaccination irrespective of dose and age groups. The neutralizing antibody against wild-type SARS-CoV-2 peaked at 14 days post the second vaccination in both 20µg and 40µg ReCOV groups, with GMT of 1643.17 IU/mL and 1289.21 IU/mL among younger adults, and 1122.32 IU/mL and 680.31 IU/mL among older adults, respectively. Similarly, both anti-RBD and anti-NTD specific IgG were elicited after the first vaccination, and peaked at 14 days after the second vaccination. T helper 1 biased cellular responses were observed after ReCOV vaccinations. Interpretation Both 20 and 40µg ReCOV showed good safety profiles and elicited strong immune responses in the younger and the older adults. The results of this study support the accelerated development of ReCOV. Funding Jiangsu Recbio Technology Co., Ltd.

14.
Hum Vaccin Immunother ; 18(5): 2055373, 2022 Nov 30.
Article in English | MEDLINE | ID: covidwho-1784265

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants have been reported to be resistant to several neutralizing antibodies (NAbs) targeting Receptor Binding Domain (RBD) and N Terminal Domain (NTD) of spike (S) protein and thus inducing immune escape. However, fewer studies were carried out to investigate the neutralizing ability of S2-specific antibodies. In this research, 10 monoclonal antibodies (mAbs) targeting SARS-CoV-2 S2 subunit were generated from Coronavirus Disease 2019 (COVID-19) convalescent patients by phage display technology and molecular cloning technology. The binding activity of these S2-mAbs toward SARS-CoV-2 S, SARS-CoV-2 S2, SARS-CoV-2 RBD, SARS-CoV-2 NTD, severe acute respiratory syndrome coronavirus (SARS-CoV) S, SARS-CoV S2 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) S proteins were evaluated by enzyme-linked immunosorbent assay (ELISA). Their neutralizing potency toward SARS-CoV-2 wild-type (WT), B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.1 and B.1.621 variants were determined by pseudo-virus-based neutralization assay. Results showed that S2E7-mAb had cross-activity to S or S2 proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, while with limited neutralizing activity to pseudo-viruses of SARS-CoV-2 WT and variants. It is undeniable that the binding and neutralizing activities of the S2-targeting mAbs are significantly weaker than the previously reported antibodies targeting RBD and NTD, but our study may provide some evidences for understanding immune protection and identifying targets for vaccine design based on the conserved S2 subunit.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Humans , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
15.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329517

ABSTRACT

Background: Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001). Methods and Findings We did a randomized, observer-blinded, placebo-controlled trial in healthy adults previously received one dose of Convidecia. Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. For both regimens, all participants received the 2nd injection with ZF2001 at 4 months after a dose of ZF2001 or TIV, with three-dose schedules of Convidecia/Convidecia/ZF2001 at day 0, day 28 and month 5 (referred to as CV/ZF/ZF (D0-D28-M5)) and CV/ZF/ZF (D0-D56-M6), and two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6). The primary outcome was the geometric mean titer (GMT) of the neutralizing antibodies against live SARS-CoV-2 virus 14 days after each boost vaccination. The safety outcome was 7-day reactogenicity, measured as solicited local or systemic adverse reactions after each vaccination. Between April 7, 2021, and May 6, 2021, 120 participants were enrolled, among whom 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 28-day interval, and 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 56-day interval. 113 (94.2%) participants received the 2nd injection with ZF2001 4 months after a dose of ZF2001 or TIV. A total of 26 participants (21.7%) reported solicited adverse events within 7 days post boost vaccinations, and all the reported adverse reactions were mild . Among participants receiving ZF001 as second dose, the GMTs of neutralizing antibodies increased to 58.4 IU/ml (42.8-79.8) in 0-28 regimen, and to 80.8 IU/ml (53.1-122.9) in 0-56 regimen at 14 days post first boost dose. The GMTs of neutralizing antibodies increased to 334.9 IU/ml (95% CI 230.4, 486.9) in C/Z/Z (D0-D28-M5) regimen, and 441.2 IU/ml (260.8, 746.4) in C/Z/Z (D0-D56-M6) regimen at 14 days after the third dose. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced comparable antibody level comparable with that elicited by three-dose schedules, with the GMTs of 282.9 IU/ml (142.5, 561.8) and 293.9 IU/ml (137.6, 627.9), respectively. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron. Conclusions Heterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating viral vectored vaccines and recombinant protein vaccine. Trial Registration ClinicalTrial.gov NCT04833101

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325403

ABSTRACT

An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Data from the U.S. NCT04368728 and German EudraCT 2020-001038-36 vaccine trials was recently reported, showing the safety, tolerability, and antibody response of the BNT162b1 vaccine candidate. BNT162b1 encodes the SARS-CoV-2 spike glycoprotein receptor-binding domain and is one of several RNA-based SARS-CoV-2 vaccine candidates under study. Here, we report preliminary results from a Phase I trial testing BNT162b1 in 144 healthy Chinese participants. The safety profile was broadly comparable to that seen in the American and German trials, with fever the only Grade 3 adverse event reported. Prime-boost vaccination with 10 µg or 30 µg BNT162b1 induced robust antibody responses in both younger (18 to 55 years of age) and older (65 to 85) Chinese adults, and interferon-γ T-cell responses to RBD antigen challenge were significantly higher in participants receiving BNT162b1 than those in placebo groups. The 30 µg dose induced increased reactogenicity as well as a more favorable vaccine-elicited virus-neutralizing response than the 10 µg dose in both younger and older Chinese adults. In conclusion, this first report of an mRNA vaccine in an Asian population showed similar results to BNT162b1 trials. This trial was funded by Fosun and BioNTech and registered under ChiCTR2000034825 and NCT04523571.

17.
Nat Med ; 28(2): 401-409, 2022 02.
Article in English | MEDLINE | ID: covidwho-1655605

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of vaccine-elicited neutralizing antibodies suggests that additional coronavirus disease 2019 (COVID-19) vaccine doses may be needed for individuals who initially received CoronaVac. We evaluated the safety and immunogenicity of the recombinant adenovirus type 5 (AD5)-vectored COVID-19 vaccine Convidecia as a heterologous booster versus those of CoronaVac as homologous booster in adults previously vaccinated with CoronaVac in an ongoing, randomized, observer-blinded, parallel-controlled phase 4 trial ( NCT04892459 ). Adults who had received two doses of CoronaVac in the past 3-6 months were vaccinated with Convidecia (n = 96) or CoronaVac (n = 102). Adults who had received one dose of CoronaVac in the past 1-3 months were also vaccinated with Convidecia (n = 51) or CoronaVac (n = 50). The co-primary endpoints were the occurrence of adverse reactions within 28 d after vaccination and geometric mean titers (GMTs) of neutralizing antibodies against live wild-type SARS-CoV-2 virus at 14 d after booster vaccination. Adverse reactions after vaccination were significantly more frequent in Convidecia recipients but were generally mild to moderate in all treatment groups. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. These data suggest that heterologous boosting with Convidecia following initial vaccination with CoronaVac is safe and more immunogenic than homologous boosting.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adenoviridae/immunology , Adolescent , Adult , COVID-19/immunology , COVID-19/prevention & control , China , Female , Humans , Immunization, Secondary , Immunoglobulin G/blood , Injection Site Reaction/pathology , Male , Middle Aged , T-Lymphocytes/immunology , Vaccination , Vaccines, Inactivated/immunology , Young Adult
20.
Chin Med J (Engl) ; 134(17): 2037-2044, 2021 Aug 02.
Article in English | MEDLINE | ID: covidwho-1480004

ABSTRACT

ABSTRACT: With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the importance of vaccines in epidemic prevention and public health has become even more obvious than ever. However, the emergence of multiple severe acute respiratory syndrome coronavirus 2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines. Here, we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them. In addition, we further discuss future directions for the research and development of the next generation of COVID-19 vaccines. We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines, including the thromboembolism caused by the AstraZeneca and Johnson & Johnson vaccines.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2
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