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2.
Emerg Microbes Infect ; 11(1): 212-226, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1585243

ABSTRACT

The recent emergence of COVID-19 variants has necessitated the development of new vaccines that stimulate the formation of high levels of neutralizing antibodies against S antigen variants. A new strategy involves the intradermal administration of heterologous vaccines composed of one or two doses of inactivated vaccine and a booster dose with the mutated S1 protein (K-S). Such vaccines improve the immune efficacy by increasing the neutralizing antibody titers and promoting specific T cell responses against five variants of the RBD protein. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that both administration schedules (i.e. "1 + 1" and "2 + 1") ensured protection against this strain. These results suggest that the aforementioned strategy is effective for protecting against new variants and enhances the anamnestic immune response in the immunized population.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CHO Cells , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Chlorocebus aethiops , Cricetulus , Female , Humans , Macaca mulatta , Mice , Mice, Transgenic , Vaccination , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vero Cells
3.
Clin Infect Dis ; 73(11): e3949-e3955, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561940

ABSTRACT

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Double-Blind Method , Humans , Immunogenicity, Vaccine
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295297

ABSTRACT

The recent emergence of new variants in the COVID-19 pandemic has led to new requirements for vaccines, with a focus on the capacity of vaccines to elicit high levels of neutralizing antibodies with specific recognition of S antigen variants based on the characterized vaccines licensed for use. A new strategy involving a heterologous vaccine composed of one or two doses of inactivated vaccine and a boost with the S1 protein with mutations (K-S) administered via the intradermal route was designed in this work and was found to improve immune efficacy by increasing neutralizing antibody titers and promoting specific T cell responses against 5 variants of the RBD peptide. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that the both schedules of “1+1” and “2+1” administration ensured a clinical protective effect against this strain. All of these results not only suggested the feasibility of our strategy for protecting against new variants but also provided a technical pathway to enhance the anamnestic immune response in the immunized population.

5.
Emerg Microbes Infect ; 10(1): 2194-2198, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1504286

ABSTRACT

Inactivated coronaviruses, including severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), as potential vaccines have been reported to result in enhanced respiratory diseases (ERDs) in murine and nonhuman primate (NHP) pneumonia models after virus challenge, which poses great safety concerns of antibody-dependent enhancement (ADE) for the rapid wide application of inactivated SARS-CoV-2 vaccines in humans, especially when the neutralizing antibody levels induced by vaccination or initial infection quickly wane to nonneutralizing or subneutralizing levels over the time. With passive transfer of diluted postvaccination polyclonal antibodies to mimic the waning antibody responses after vaccination, we found that in the absence of cellular immunity, passive infusion of subneutralizing or nonneutralizing anti-SARS-CoV-2 antibodies could still provide some level of protection against infection upon challenge, and no low-level antibody-enhanced infection was observed. The anti-SARS-CoV-2 IgG-infused group and control group showed similar, mild to moderate pulmonary immunopathology during the acute phase of virus infection, and no evidence of vaccine-related pulmonary immunopathology enhancement was found. Typical immunopathology included elevated MCP-1, IL-8 and IL-33 in bronchoalveolar lavage fluid; alveolar epithelial hyperplasia; and exfoliated cells and mucus in bronchioles. Our results corresponded with the recent observations that no pulmonary immunology was detected in preclinical studies of inactivated SARS-CoV-2 vaccines in either murine or NHP pneumonia models or in large clinical trials and further supported the safety of inactivated SARS-CoV-2 vaccines.


Subject(s)
Antibodies, Viral/immunology , Antibody-Dependent Enhancement , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Alveolar Epithelial Cells/pathology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/toxicity , Bronchioles/chemistry , Bronchioles/pathology , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , COVID-19/pathology , COVID-19/virology , Cytokines/analysis , Humans , Hyperplasia , Immunoglobulin G/immunology , Immunoglobulin G/toxicity , Lung/pathology , Macaca mulatta , Male , Mice , Mucus , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Vaccines, Inactivated/immunology
6.
Vaccine ; 39(48): 6980-6983, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1475113

ABSTRACT

In clinical trials, antibodies against SARS-CoV-2 were almost eliminated in participants six months after immunization with an inactivated SARS-CoV-2 vaccine. The short duration of antibody persistence is an urgent problem. In this study, the problem was solved by intradermal inoculation with trace antigen. Within 72 h after intradermal inoculation, slight inflammatory reactions, such as redness and swelling, were observed at the inoculation site of the participants. On the 7th, 60th and 180th days after inoculation, the antibodies of the participants were detected, and it was found that the neutralizing antibody and ELISA (IgGs) anti-S antibody levels rapidly increased and were maintained for 6 months. These results indicate that there was a SARS-CoV-2-specific immune response in the participants immunized with an inactivated SARS-CoV-2 vaccine, which could be quickly and massively activated by intradermal trace antigen inoculation to produce an effective clinically protective effect.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Humans , SARS-CoV-2
7.
Mol Ther Methods Clin Dev ; 23: 108-118, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1379195

ABSTRACT

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

8.
Emerg Microbes Infect ; 10(1): 1112-1115, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1246664

ABSTRACT

Neutralizing antibodies in the subjects of an inactivated SARS-CoV-2 vaccine clinical trial showed a decreasing trend over months. An investigation studying the third immunization suggested that the waning of neutralizing antibodies in individuals administered two doses of inactivated vaccine does not mean the disappearance of immunity.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunization, Secondary , Immunologic Memory , Adolescent , Adult , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/administration & dosage , Humans , Middle Aged , Vaccination/statistics & numerical data , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Young Adult
9.
J Med Virol ; 93(2): 892-898, 2021 02.
Article in English | MEDLINE | ID: covidwho-1206802

ABSTRACT

Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID-19), the immunogenicity of spike protein-based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor-binding domain (RBD) and more efficiently neutralized SARS-CoV-2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID-19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1-based subunit COVID-19 vaccines to reduce the potential risk of antibody-dependent enhancement of infection.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Antigens, Viral/immunology , COVID-19 Vaccines/biosynthesis , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/administration & dosage , Alum Compounds/administration & dosage , Animals , Antigens, Viral/genetics , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , HEK293 Cells , Humans , Immunity, Humoral/drug effects , Immunization , Immunization Schedule , Immunogenicity, Vaccine , Immunoglobulin A/biosynthesis , Immunoglobulin G/biosynthesis , Mice , Mice, Inbred BALB C , Protein Domains/immunology , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology
10.
Food Chem Toxicol ; 152: 112239, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1202176

ABSTRACT

The outbreak of COVID-19 has posed a serious threat to global public health. Vaccination may be the most effective way to prevent and control the spread of the virus. The safety of vaccines is the focus of preclinical research, and the repeated dose toxicity test is the key safety test to evaluate the vaccine before clinical trials. The purpose of this study was (i) to observe the toxicity and severity of an inactivated SARS-CoV-2 vaccine (Vero cells) in rodent Sprague Dawley rats after multiple intramuscular injections under the premise of Good Laboratory Practice principles and (ii) to provide a basis for the formulation of a clinical trial scheme. The results showed that all animals in the experimental group were in good condition, no regular changes related to the vaccine were found in the detection of various toxicological indexes, and no noticeable stimulating reaction related to the vaccine was found in the injected local tissues. The neutralizing antibodies in the low- and high-dose vaccine groups began to appear 14 days after the last administration. In the negative control group, no neutralizing antibodies were observed from the administration period to the recovery period. Therefore, the repeated administration toxicity test of the inactivated SARS-CoV-2 vaccine (Vero cells) in Sprague Dawley rats showed no obvious toxic reaction. It was preliminarily confirmed that the vaccine can stimulate production of neutralizing antibodies and is safe in Sprague Dawley rats.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Animals , COVID-19 , COVID-19 Vaccines/toxicity , Female , Male , Rats, Sprague-Dawley , Toxicity Tests , Vaccines, Inactivated/immunology , Vaccines, Inactivated/toxicity
11.
Vaccine ; 39(20): 2746-2754, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1174522

ABSTRACT

BACKGROUND: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. METHOD: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated. RESULTS: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine. INTERPRETATION: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. TRIAL REGISTRATION: CTR20200943 and NCT04412538.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccines , Adolescent , Adult , Antibodies, Viral , China , Double-Blind Method , Humans , Immunogenicity, Vaccine , Middle Aged , SARS-CoV-2 , Young Adult
13.
PLoS Pathog ; 16(11): e1008949, 2020 11.
Article in English | MEDLINE | ID: covidwho-922716

ABSTRACT

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1ß), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1ß/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Animals , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cytokines/immunology , Disease Models, Animal , Lung/immunology , Lung/pathology , Macaca mulatta , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Load/methods , Virulence , Virus Shedding
14.
J Cell Mol Med ; 24(24): 14270-14279, 2020 12.
Article in English | MEDLINE | ID: covidwho-907630

ABSTRACT

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few studies have focused on the changes of NK, T- and B-cell subsets, inflammatory cytokines and virus-specific antibodies in patients with moderate COVID-19. A total of 11 RT-PCR-confirmed convalescent patients with COVID-19 and 11 patients with non-SARS-CoV-2 pneumonia (control patients) were enrolled in this study. NK, CD8+ T, CD4+ T, Tfh-like and B-cell subsets were analysed using flow cytometry. Cytokines and SARS-CoV-2-specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID-19 than in control patients (P = 0.017). Effector memory CD8+ T-cell counts significantly increased in patients with COVID-19 during a convalescent period of 1 week (P = 0.041). TIM-3+ Tfh-like cell and CD226+ Tfh-like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS+ Tfh-like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS-CoV-2. The increase in effector memory CD8+ T-cell counts, the up-regulation of inhibitory molecules and the down-regulation of active molecules on CD4+ T cells and Tfh-like cells in patients with COVID-19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID-19.


Subject(s)
Antibodies, Viral/biosynthesis , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Cytokines/biosynthesis , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , T Follicular Helper Cells/immunology , Adult , Aged , Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/epidemiology , China/epidemiology , Cytokines/immunology , Female , Humans , Male , Middle Aged , Young Adult
15.
J Med Virol ; 92(11): 2830-2838, 2020 11.
Article in English | MEDLINE | ID: covidwho-848038

ABSTRACT

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the angiotensin-converting enzyme 2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although messenger RNA expression of various innate immune signaling molecules is altered in the cells, transcription of interferons-α (IFN-α), IFN-ß, and IFN-γ is unchanged. Furthermore, expression of some interleukins (IL) related to inflammatory reactions, such as IL-6, IL-2, and IL-8, is maintained at low levels, whereas that of ILs involved in immune regulation is upregulated. Interestingly, IL-22, an IL that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism.


Subject(s)
Bronchi/cytology , Epithelial Cells/virology , SARS-CoV-2/physiology , Virus Replication , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Cell Line , Cytopathogenic Effect, Viral/immunology , Epithelial Cells/immunology , Humans , Immunity, Innate , Interleukins/immunology , Spike Glycoprotein, Coronavirus/metabolism
16.
PeerJ ; 8: e10018, 2020.
Article in English | MEDLINE | ID: covidwho-832749

ABSTRACT

BACKGROUND: Older adults have been reported to be a population with high-risk of death in the COVID-19 outbreak. Rapid detection of high-risk patients is crucial to reduce mortality in this population. The aim of this study was to evaluate the prognositc accuracy of the Modified Early Warning Score (MEWS) for in-hospital mortality in older adults with COVID-19. METHODS: A retrospective cohort study was conducted in Wuhan Hankou Hospital in China from 1 January 2020 to 29 February 2020. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of MEWS, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Function Assessment (SOFA), quick Sequential Organ Function Assessment (qSOFA), Pneumonia Severity Index (PSI), Combination of Confusion, Urea, Respiratory Rate, Blood Pressure, and Age ≥65 (CURB-65), and the Systemic Inflammatory Response Syndrome Criteria (SIRS) for in-hospital mortality. Logistic regression models were performed to detect the high-risk older adults with COVID-19. RESULTS: Among the 235 patients included in this study, 37 (15.74%) died and 131 (55.74%) were male, with an average age of 70.61 years (SD 8.02). ROC analysis suggested that the capacity of MEWS in predicting in-hospital mortality was as good as the APACHE II, SOFA, PSI and qSOFA (Difference in AUROC: MEWS vs. APACHE II, -0.025 (95% CI [-0.075 to 0.026]); MEWS vs. SOFA, -0.013 (95% CI [-0.049 to 0.024]); MEWS vs. PSI, -0.015 (95% CI [-0.065 to 0.035]); MEWS vs. qSOFA, 0.024 (95% CI [-0.029 to 0.076]), all P > 0.05), but was significantly higher than SIRS and CURB-65 (Difference in AUROC: MEWS vs. SIRS, 0.218 (95% CI [0.156-0.279]); MEWS vs. CURB-65, 0.064 (95% CI [0.002-0.125]), all P < 0.05). Logistic regression models implied that the male patients (≥75 years) had higher risk of death than the other older adults (estimated coefficients: 1.16, P = 0.044). Our analysis further suggests that the cut-off points of the MEWS score for the male patients (≥75 years) subpopulation and the other elderly patients should be 2.5 and 3.5, respectively. CONCLUSIONS: MEWS is an efficient tool for rapid assessment of elderly COVID-19 patients. MEWS has promising performance in predicting in-hospital mortality and identifying the high-risk group in elderly patients with COVID-19.

17.
J Med Virol ; 93(2): 892-898, 2021 02.
Article in English | MEDLINE | ID: covidwho-661060

ABSTRACT

Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID-19), the immunogenicity of spike protein-based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor-binding domain (RBD) and more efficiently neutralized SARS-CoV-2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID-19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1-based subunit COVID-19 vaccines to reduce the potential risk of antibody-dependent enhancement of infection.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Antigens, Viral/immunology , COVID-19 Vaccines/biosynthesis , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/administration & dosage , Alum Compounds/administration & dosage , Animals , Antigens, Viral/genetics , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , HEK293 Cells , Humans , Immunity, Humoral/drug effects , Immunization , Immunization Schedule , Immunogenicity, Vaccine , Immunoglobulin A/biosynthesis , Immunoglobulin G/biosynthesis , Mice , Mice, Inbred BALB C , Protein Domains/immunology , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology
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