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The widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron; and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.
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Zinc is one of the essential trace elements for human. It is essential for human health. In recent decades, the distribution and transport of zinc in human body have gradually become more evident. The immunomodulatory effects of zinc on the immune system have also been elucidated. Zinc is involved in regulating the cellular signaling pathways of immune cells and affecting the development of immune organs, the physiological state and function of immune cells and the secretion of cytokines. It is an indispensable element in the immune system and plays an important role in maintaining the integrity and stability of the immune system. This article briefly introduced the distribution and transportation of zinc in the human body, with the emphasis on the relationship between zinc and the development and function of immune cells.
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Human coronavirus OC43 (HCoV-OC43) and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) belong to the β-coronavirus genus. Since the discovery in 1967, HCoV-OC43 has been continuously circulating in human population and has become one of the common seasonal respiratory viruses. SARS-CoV-2, which has a higher morbidity and fatality rate, appeared at the end of 2019, followed by the emergence of a variety of variants, and the transmission and infection capacity of SARS-CoV-2 has been enhanced. HCoV-OC43 may be similar to SARS-CoV-2 in terms of genomic structure and function, species evolution, epidemic characteristics and clinical manifestations. In this review, the epidemiology, genomics, phylogenetic evolution and other aspects of HCoV-OC43 and SARS-CoV-2 were analyzed. Such an analysis would be helpful to understand the association and differences between the two viruses, and provide reference for understanding the potential threats of HCoV-OC43.
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Chronic hepatitis B (CHB) is often treated with drugs such as interferons and nucleoside (acid)/nucleotide (acid) analogs. While these drugs are effective in controlling the viral loads, they are not able to eliminate hepatitis B virus (HBV) from the body completely. Besides, side effects and drug resistance may by caused by the long-term use of these drugs. Several monoclonal antibodies (McAbs) against HBV, mostly against hepatitis B surface antigen (HBsAg), have been demonstrated with viral neutralization capability and with effective inhibition of HBV replication in relevant animal models. The use of a McAb individually or in combination with another therapy has the potentials to achieve functional cure of CHB. In this review, we summarized the encouraging results from the research and development of anti-HBV McAbs in clinical or pre-clinical development stage, aiming to provide new idea for the treatment of CHB.
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A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.
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Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins--receptor binding domain (RBD), S1 subunit and S ectodomain--in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 [A] proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.
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Objective To evaluate the immunostimulatory effects of polysaccharides, including Lycium barbarum polysaccharides ( LBP) , Angelica polysaccharides ( AP) , Licorice polysaccharides ( LP) and Inulin polysaccharides ( IP) , used alone or in combination with aluminum adjuvant on the recombinant protein of varicella-zoster virus (VZV) glycoprotein (gE) as an immunogen in mice. Methods BALB/c mice were randomly divided into 11 groups with five in each group. Intramuscular injection was given at Days 0 and 14. Serum samples were collected at weeks 0, 2, 3, 4 and detected for total anti-gE IgG titers and an-tibody subtypes by indirect ELISA. The mice were sacrificed at week 4 to collect spleen lymphocytes aseptic-ally. CCK-8 method was used to evaluate the proliferation of spleen lymphocytes. The levels of IFN-γ and IL-4 were measured by ELISA. The percentages of CD3+CD4+ and CD3+CD8+ T cell subsets were deter-mined by flow cytometry. Results The four plant-derived polysaccharides in combination with aluminum adjuvant showed good adjuvant activities. LP combined with aluminum adjuvant effectively increased the titer of IgG2, promote the proliferation of splenocytes and enhanced the secretion of IFN-γ and IL-4. Further-more, it also induced CD3+CD4+ and CD3+CD8+ T cell proliferation in vivo. Conclusions The four plant-derived polysaccharides in combination with aluminum adjuvant could all enhance antibody production. LP combined with aluminum adjuvant could induce cell-mediated immune responses, suggesting that it might be a promising adjuvant for varicella-zoster subunit vaccines.
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Monoclonal antibody (mAb)-based therapeutics are playing an increasingly important role in the treatment or prevention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multi-domain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-translational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase as well as post licensure life cycle management. Specially, the molecular characterization, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parameters and the methods used for obtaining them. The three groups of analytical methods are three essential and integral facets making up the whole analytical package for a mAb-based drug. Such a package is critically important for the licensure and the post-licensure life cycle management of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilar mAbs were discussed briefly based on the recommendations by the World Health Organization.
Subject(s)
Animals , Humans , Antibodies, Monoclonal , Chemistry , Therapeutic Uses , Biological Products , Therapeutic Uses , Glycosylation , Kinetics , LigandsABSTRACT
Objective@#This study aims to evaluate the prevention effect and cost-effectiveness of a prophylactic bivalent human papilloma virus (HPV) vaccine.@*Methods@#A multiple health status dynamic model was developed, including natural history of diseases and prevention strategies. We built 19 prevention strategies including visual inspection with acetic acid/lugol's iodine (VIA/VILI) and/or 3 does prophylactic bivalent HPV vaccine administered to adolescent girls at the age of 15 years old every year under the assumption that vaccine coverage and screening coverage were 70%. The incremental cost-effectiveness ratio (ICER), optimal price of 3 does vaccine and cost-effectiveness frontier of these strategies were analyzed compared with no-intervention. The ICER threshold is 152 087 CNY.@*Results@#Compared with no-intervention, Routine vaccination reduced the incidence of cervical cancer by 69.5%, superior to 5 strategies including VIA/VILI screening only. The range of effect was between 9.0% and 69.2%, and the effect of strategy increased significantly with the increase of screening frequency. Combination vaccination with screening at ages of 35 reduced the incidence of cervical cancer by 72.0%, and the effect increased with the increase of screening frequency. Combination vaccination with screening every 3 years between (35-64) years old reduced the incidence by 89.4%. Compared with no-intervention, the ICER of combination vaccination with screening twice between 35 years and 64 years was 121 292 CNY/life-year, which was cost-effective. The price of vaccine had a significant impact on the ICER of the strategy; when the vaccine price was less than 600 CNY, only routine vaccination or supplementary vaccination between 16-39 years old after routine vaccination was cost-effective; when the vaccine price was less than 1 200 CNY, supplementary vaccination between 16-19 years old plus VIA/VILI was cost-effective.@*Conclusion@#Ther prevention strategy was cost-effective, which could effectively reduce the incidence of cervical cancer by implementation of HPV vaccination combined with VIA/VILI in suitable aging females.
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Cervical carcinoma has brought huge burden on patients, especially in developing countries. Preventive vaccines could effectively reduce the incidence of cervical carcinoma. The high prices were one of the most difficult problem in introducing the vaccine in developing countries, so the cost-effectiveness and health financing of the vaccines should be carefully studied before incorporated into the national immunization program. Thus, researchers used mathematical models to predict the effects of HPV vaccines and to study the cost- effectiveness. In order to understand the current situation on the cost-effectiveness of HPV vaccines in the developing countries, a systematic searching of literature from PubMed, Elsevier Science Direct, Medline, ProQuest, CNKI and Wangfang Data was performed, this study aims to conduct a systematic review from aspects of project source, first author, research areas, research perspectives, prevention strategies, vaccine characteristics, cost-effectiveness.
Subject(s)
Female , Humans , Cost-Benefit Analysis , Developing Countries , Immunization Programs , Incidence , Models, Theoretical , Papillomavirus Infections , Economics , Papillomavirus Vaccines , Economics , Uterine Cervical Neoplasms , EconomicsABSTRACT
Adjuvants have been used as critical components of vaccine.They were used to stabilize the antigens and potentiate the immune responses.Dose sparing is also of interests in recent years to be applied in potential pandemic situations or to lower the costs of vaccines.With the emerging nanotechnology in many aspects including the use in biomedical applications,the application of nanomaterials as vaccine adjuvants also attracted a lot of attentions in recent years.With favorable biological properties,such as well-defined and well-formed nanoparticles,biocompatibility,biodegradability and ability to induce humoral immunity and cellular immunity simultaneously,calcium phosphate nanoparticles (CaP) have the potentials to be developed as an immune potentiator to be used as vaccine adjuvants.Here,we reviewed the basic properties of CaP and their applications as vaccine adjuvants with antigens of different modalities such as inactivated virus,protein and naked DNAs.The mechanism of the adjuvanting effects is briefly described.Further the development of CaP as vaccine adjuvants with some designed surface modification could lead to next generation vaccine adjuvants with improved immune potentiating properties and safety profiles.
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Zika fever is a self-limiting and acute infectious disease caused by Zika virus infection. It is mainly transmitted through the bite of mosquitoes of the Aedes type. It can also be spread through verti-cal transmission. There is evidence that it can also be sexually transmitted from a man to his sex partners due to the presence of the virus in semen. The re-emergence of the virus in 2015 as a major endemic in the South American countries ( which may spread further) warrants better understanding of Zika virus. The outbreaks, transmission routes, virological characteristics and the diagnosis and treatment of Zika virus infection will be summarized in this review. Moreover, the potential correlations between newborn microcephaly and Zika vi-rus infection as well as the possible molecular mechanisms for causing microcephaly such as cell autophagy will also be discussed.
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Objective To quantitatively analyze the characteristics of a panel of murine anti-human papillomavirus(HPV)11 L1-derived virus-like particle( VLP ) monoclonal antibodies ( mAbs ) and establish the mAb-based methods for antigen quality analysis.Methods A panel of 22 murine anti-HPV11 mAbs were characterized in details with their isotype, and binding affinity, conformational sensitivity were examined quantitatively in the direct binding ELISA and Western blot.The hemagglutination inhibition activity of mAbs were identified using the hemagglutination inhibition assay and the pseudovirus ( PsV ) neutralization efficiency were examined quantitatively using the PsV-based neutralization assay.The type-specific, highly conformational sensitive and neutralizing mAbs were selected to be used in the sandwich ELISA assay.Results Based on the quantitative and semi-quantitative results, six type-specific, highly conformational sensitive and neutralizing mAbs (2A2, 4A1-3, 16G7, 14A6, 9C1 and 19C7) were identified.These mAbs, along with 10D6 were screened as the capture mAb or as the detection mAb in the sandwich ELISA.Conclusion The binding affinity, conformational sensitivity and neutralization efficiency of anti-HPV11 mAbs were characterized in details.A mAb-based sandwich ELISA assay (14A6:Ag:9C12-HRP) were developed, which could be used in the in vitro potency analysis of HPV11 VLP-based vaccine.
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John Cunningham virus(JCV)is a type of human polyomavirus. It was first isolated from the brain of a patient with progressive multifocal leukoencephalopathy(PML)in 1971 and named after that patient. The seroprevalence of JCV in the general population is 40% to 60% . The mortality rate among patients with AIDS complicated by PML was shown to be 50% . For immunocompromised patients and pa-tients with long-term use of immunosuppressive drugs,JCV would cause fatal polyomavirus associated ne-phropathy(PVAN),viremia and some other related diseases. While the pathogenesis of JCV has well stud-ied,there are no specific prevention and treatment measures for infected individuals. Therefore,reliable, specific and sensitive JCV detection methods in clinical settings are needed. This review describes the pros and cons of different methods for JCV detection with potentials for clinical applications.
