ABSTRACT
Background and aims: Although COVID-19 vaccination is recommended for the patients with chronic liver disease, the clinical outcomes of COVID-19 vaccinated in patients with chronic hepatitis B (CHB) has not been well characterized. The study aimed to explore the safety and specific antibody responses following COVID-19 vaccination among CHB patients. Methods: Patients with CHB were included. All patients were vaccinated with two doses of inactivated vaccine (CoronaVac) or three doses of adjuvanted protein subunit vaccine (ZF2001). The adverse events were recorded and neutralizing antibody (NAb) were determined 14 days following the whole-course vaccination. Results: A total of 200 patients with CHB were included. Specific NAb against SARS-CoV-2 were positive in 170 (84.6%) patients. The median (IQR) concentrations of NAb were 16.32 (8.44-34.10) AU/ml. Comparison of immune responses between CoronaVac and ZF2001 vaccines showed no significant differences in neither the concentrations of NAb nor the seropositive rates (84.4 vs. 85.7%). Moreover, we observed lower immunogenicity in older patients and in patients with cirrhosis or underlying comorbidities. The incidences of adverse events were 37 (18.5%) with the most common adverse event as injection side pain [25 (12.5%)], followed by fatigue [15 (7.5%)]. There were no differences in the frequencies of adverse between CoronaVac and ZF2001 (19.3% vs. 17.6%). Almost all of the adverse reactions were mild and self-resolved within a few days after vaccination. Severe adverse events were not observed. Conclusions: COVID-19 vaccines, CoronaVac and ZF2001 had a favorable safety profile and induced efficient immune response in patients with CHB.
ABSTRACT
The SARS-CoV-2 Omicron variants of concern (VOCs) showed severe resistance to the early-approved COVID-19 vaccines-induced immune responses. The breakthrough infections by the Omicron VOCs are currently the major challenge for pandemic control. Therefore, booster vaccination is crucial to enhance immune responses and protective efficacy. Previously, we developed a protein subunit COVID-19 vaccine ZF2001, based on the immunogen of receptor-binding domain (RBD) homodimer, which was approved in China and other countries. To adapt SARS-CoV-2 variants, we further developed chimeric Delta-Omicron BA.1 RBD-dimer immunogen which induced broad immune responses against SARS-CoV-2 variants. In this study, we tested the boosting effect of this chimeric RBD-dimer vaccine in mice after priming with two doses of inactivated vaccines, compared with a booster of inactivated vaccine or ZF2001. The results demonstrated that boosting with bivalent Delta-Omicron BA.1 vaccine greatly promoted the neutralizing activity of the sera to all tested SARS-CoV-2 variants. Therefore, the Delta-Omicron chimeric RBD-dimer vaccine is a feasible booster for those with prior vaccination of COVID-19 inactivated vaccines.
Subject(s)
COVID-19 , Carrier Proteins , Animals , Humans , Mice , COVID-19 Vaccines , SARS-CoV-2 , Protein Subunits , COVID-19/prevention & control , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
Objectives. Since the outbreak of SARS-CoV-2 in late 2019, nearly 12.2 billion doses of the COVID-19 vaccine have been administered worldwide; however, the humoral immune responses induced by different types of vaccines are yet to be fully validated. Methods. We analyzed antibody levels in 100 serum samples after vaccination with different types of COVID-19 vaccines and their reactivity against the RBD antigen of Delta and Omicron variants using a bead-based microarray. Results. Elevated levels of anti-wild-type (WT)-RBD IgG and anti-WT-NP IgG were detected in participants who received two doses of the inactivated vaccines (CoronaVac or BBIBP-CorV) and three doses of the recombinant spike protein vaccine (ZF2001), indicating that antibody responses to SARS-CoV-2 were generated regardless of the vaccine administered. We found highly correlated levels of serum anti-RBD IgG and anti-NP IgG (r = 0.432, p < 0.001). We observed that the antibodies produced in vivo after COVID-19 vaccination still reacted with variants of SARS-CoV-2 (p < 0.0001). Conclusions. Our results show that high levels of specific antibodies can be produced after completion of COVID-19 vaccination (two doses of the inactivated vaccines or three doses of ZF2001), with some degree of cross-reactivity to the RBD antigen of Delta and Omicron variants, and provide an accessible and practical experimental method for post-vaccination antibody detection.
ABSTRACT
Although the new coronavirus disease 2019 (COVID-19) outbreak occurred in late 2019, it is still endemic worldwide, and has become a global public health problem. Vaccination against SARS-CoV-2 is considered to be the most effective intervention to prevent the spread of COVID-19. ZF2001 is a recombinant protein vaccine based on SARS-CoV-2 receptor-binding domain (RBD) subunit which contains aluminum adjuvant. In order to advance our research on ZF2001 into clinical trial, we investigated the general toxicity and immunogenicity of ZF2001 in cynomolgus monkeys and assessed the possible target organs for vaccine-induced toxicity. In the present research, we observed no significant systemic toxicities and abnormal cardiovascular and respiratory events following four times injections of intramuscular ZF2001 in cynomolgus monkeys. Histological examination revealed recoverable inflammatory changes in quadricep muscle and adjacent lymph node at the vaccine injection site. As expected, the vaccine can produce a strongly specific binding antibody and neutralizing antibodies in cynomolgus monkeys after inoculation. Taken together, our regulatory toxicology research proves the safety and immunogenicity of the ZF2001 vaccine, supporting its entry into large scale clinical trials.
ABSTRACT
To investigate the protective efficacy and mechanism of ZF2001 (a protein subunit vaccine with conditional approval in China) to SARS-CoV-2 Delta variant-induced severe pneumonia, the lethal challenge model of K18-hACE2 transgenic mice was used in this study. An inactivated-virus vaccine at the research and development stage (abbreviated as RDINA) was compared to ZF2001. We found that ZF2001 and RDINA could provide the protective effect against Delta variant-induced severe cases, as measured by the improved survival rates, the reduced virus loads, the alleviated lung histopathology and the high neutralizing antibody geomean titers, compared to aluminum adjuvant group. To prevent and control Omicron or other variant epidemics, further improvements in vaccine design and compatibilities with the novel adjuvant are required to achieve better immunogenicity.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/prevention & control , Melphalan , Mice , Mice, Transgenic , Vaccines, Inactivated , gamma-GlobulinsABSTRACT
Safe, efficacious, and deployable vaccines are urgently needed to control COVID-19 in the large-scale vaccination campaigns. We report here the preclinical studies of an approved protein subunit vaccine against COVID-19, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and non-human primates, and elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25â µg or 50â µg ZF2001 prevented infection with SARS-CoV-2 in lung, trachea, and bronchi, with milder lung lesions. No evidence of disease enhancement was observed in both animal models. ZF2001 has been approved for emergency use in China, Uzbekistan, Indonesia, and Columbia. The high safety, immunogenicity, and protection efficacy in both mice and NHPs found in this preclinical study was consistent with the results in human clinical trials.