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Advances in Zika virus vaccines and therapeutics:A systematic review

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Asian Pacific Journal of Tropical Medicine 2024年第3期17卷 97-109页

作者： Shiza Malik Khalid Muhammad Omar Ahsan Muhammad Tahir Khan Ranjit Sah Yasir Waheed Bridging Health Foundation Rawalpindi 46000Pakistan Department of Biology College of SciencesUAE University15551Al AinUnited Arab Emirates Department of Medicine Foundation University Medical CollegeFoundation University IslamabadIslamabad 44000Pakistan INTI International University Persiaran Perdana BBN Putra Nilai71800 NilaiNegeri SembilanMalaysia Institute of Molecular Biology and Biotechnology the University of LahoreKM Defence RoadLahore 58810Pakistan Zhongjing Research and Industrialization Institute of Chinese Medicine Zhongguancun Scientific ParkNanyang 473006China Department of Microbiology Tribhuvan University Teaching HospitalInstitute of MedicineKathmandu 44600Nepal Department of Microbiology Dr.D.Y.Patil Medical CollegeHospital and Research CentreDr.D.Y.Patil VidyapeethPune 411018MaharashtraIndia Department of Public Health Dentistry Dr.D.Y.Patil Dental College and HospitalDr.D.Y.Patil VidyapeethPune 411018MaharashtraIndia Gilbert and Rose-Marie Chagoury School of Medicine Lebanese American UniversityByblos 1401Lebanon

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

关键词： Zika virus Infection Therapeutics Antiviral agents vaccines Therapies Treatment Novel therapeutic Clinical management

B-cell and antibody responses to SARS-CoV-2:infection,vaccination,and hybrid immunity

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Cellular & Molecular Immunology 2024年第2期21卷 144-158页

作者： Dennis Lapuente Thomas H.Winkler Matthias Tenbusch Institut für klinische und molekulare Virologie Universitätsklinikum Erlangen und Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossgarten 491054 ErlangenGermany Department of Biology Division of GeneticsNikolaus-Fiebiger-Center for Molecular MedicineFriedrich-Alexander-Universität Erlangen-Nürnberg(FAU)ErlangenGermany Medical Immunology Campus Erlangen Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossplatz 191054 ErlangenGermany

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

关键词： SARS-CoV-2 neutralizing antibodies memory responses vaccines IgG4

Antigen epitopes of animal coronaviruses:a mini-review

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Animal Diseases 2024年第1期4卷 19-26页

作者： Mingjun Su Guanghui Zheng Xiangwen Xu Houhui Song Key Laboratory of Applied Technology On Green-Eco-Healthy Animal Husbandry of Zhejiang Province Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics&Advanced TechnologyZhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health ManagementChina-Australia Joint Laboratory for Animal Health Big Data AnalyticsCollege of Animal Science and Technology&College of Veterinary Medicine of ZhejiangA&F University666 Wusu StreetLin'an DistrictHangzhou 311300Zhejiang ProvinceChina

Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.

关键词： Animal coronavirus Antigen epitope B-cell epitope T-cell epitope Immune responses vaccines

Antimicrobial resistance containment in Africa:Moving beyond surveillance

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Biosafety and Health 2024年第1期6卷 50-58页

作者： Zikora Kizito Glory Anyaegbunam Ifeanyi Elibe Mba Yandev Doowuese Ngozi J.Anyaegbunam Toluwalase Mba Fetuata Aminat Aina Vincent NnamdigadiChigor Emeka Innocent Nweze Emmanuel A.Ezea Department of Microbiology Faculty of Biological SciencesUniversity of Nigeria Nsukka CampusEnugu 410001Nigeria Department of Pharmaceutical Microbiology Faculty of PharmacyUniversity of IbadanIbadan 20005Nigeria Department of Microbiology Federal University of Health SciencesOtukpo 970001Nigeria Measurement and Evaluation Unit Science Education Department University of Nigeria NsukkaEnugu 410001Nigeria Sumy State University Medical InstituteSumy Oblast 40000Ukraine Lead City University Hospital Lead CityIbadan 200255Nigeria Department of Microbiology College of Natural SciencesFederal University of AgricultureAbeokuta 111101Nigeria

Worldwide,infections caused by drug‐resistant pathogens constitute a significant challenge threatening therapeutic efforts.According to the World Health Organization(WHO),antimicrobial resistance(AMR)ranks among the top 10 global public health threats.Organisms with a high rate of multiple host adaptivity,significant genetic diversity(multiple lineages),high virulence factors,and genetic exchange have been isolated from various sources(humans,animals,and the environment)even without exposure to prior antibiotics.Till now,the source of AMR and how resistant clones are selected in the environment remain largely elusive,and potential anthropogenic transmission has been reported in different studies.Various drug‐resistant pathogens,lineages,resistant clones,outbreak clusters,plasmid replicates,and genes that play a critical role in resistance dissemination have been identified.Maintenance of certain multidrug‐resistant(MDR)determinants has also been shown to enhance or support the propagation of MDR.So far,significant advances have been made in understanding the burden of AMR.However,overcoming AMR requires a holistic approach,as there is no single approach with sufficient precision to curb the threat.While strengthening AMR surveillance efforts is essential,as we have shown,there is also a need to intensify efforts to strengthen therapeutic interventions,especially in priority regions such as Africa.Herein,we discussed the burden of AMR and the dissemination of AMR in humans,animals,and the environment(non‐medical drivers).We further delved into the big questions on Africa and discussed how therapeutic interventions involving vaccines and other viable biomaterials could be pivotal in reducing the burden of AMR to the barest minimum.

关键词： Antimicrobial resistance(AMR) Bacteria Surveillance One Health vaccines Africa

Multi-omics for COVID-19:driving development of therapeutics and vaccines

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National Science Review 2023年第9期10卷 307-336页

作者： Mengyu Guo Muya Xiong Jinying Peng Tong Guan Haixia Su Yanyi Huang Cai-Guang Yang Yang Li Diana Boraschi Thanigaimalai Pillaiyar Guanbo Wang Chengqi Yi Yechun Xu Chunying Chen CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory of Protein and Plant Gene Research School of Life Sciences Peking University Biomedical Pioneering Innovation Centre Peking University 6. Institute for Cell AnalysisShenzhen Bay Laboratory Peking-Tsinghua Center for Life Sciences Peking University College of Chemistry and Molecular Engineering Beijing National Laboratory for Molecular SciencesPeking University 9. State Key Laboratory of Drug Research Centre for Chemical BiologyShanghai Institute of Materia MedicaChinese Academy of Sciences 10. Laboratory of Immunology and Nanomedicine and China-Italy Joint Laboratory of Pharmacobiotechnology for Medical ImmunomodulationShenzhen Institute of Advanced TechnologyChinese Academy of Sciences 11. Institute of Biochemistry and Cell Biology National Research Council 12. Institute of PharmacyPharmaceutical/Medicinal Chemistry and Tuebingen Center for Academic Drug Discovery Eberhard Karls University Tübingen 13. Department of Chemical Biology and Synthetic and Functional Biomolecules CenterCollege of Chemistry and Molecular Engineering Peking University 14. GBA National Institute for Nanotechnology Innovation

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has raised global concern for public health and economy.The development of therapeutics and vaccines to combat this virus is continuously progressing.Multi-omics approaches,including genomics,transcriptomics,proteomics,metabolomics,epigenomics and metallomics,have helped understand the structural and molecular features of the virus,thereby assisting in the design of potential therapeutics and accelerating vaccine development for COVID-19.Here,we provide an up-to-date overview of the latest applications of multi-omics technologies in strategies addressing COVID-19,in order to provide suggestions towards the development of highly effective knowledge-based therapeutics and vaccines.

关键词： COVID-19 SARS-CoV-2 multi-omics antibodies small-molecule drugs vaccines

USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID

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Signal Transduction and Targeted Therapy 2022年第2期7卷 451-465页

作者： Yuewen Luo Xiantao Zhang Ran Chen Rong Li Yang Liu Junsong Zhang Qin liu Meijun Si Jun Liu Bolin Wu Xuemei Wang Shijian Wu Yiwen Zhang Xu Zhang Deyin Guo Xin He Ting Pan Hui Zhang Institute of Human Virology Key Laboratory of Tropical Disease Control of Ministry of EducationGuangdong Engineering Research Center for Antimicrobial Agent and ImmunotechnologyZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China School of Medicine Sun Yat-sen UniversityGuangzhou/Shenzhen 510080China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhouChina Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhouGuangdongChina Guanghua School of Stomatology Hospital of StomatologySun Yat-sen UniversityGuangdong Provincial Key Laboratory of StomatologyGuangzhou 510060 GuangdongChina National Guangzhou Laboratory Bio-IslandGuangzhouGuangdong 510320China

Activation-induced cytidine deaminase(AID)initiates class-switch recombination and somatic hypermutation(SHM)in antibody genes.Protein expression and activity are tightly controlled by various mechanisms.However,it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works.Here,we demonstrated that a deubiquitinase USP10,which specifically stabilizes nuclear AID protein,can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain.Interestingly,the signals from BCR and TLR1/2 synergistically promoted this phosphorylation.The deficiency of USP10 in B cells significantly decreased AID protein levels,subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)or human immunodeficiency virus type 1(HIV-1)nanoparticle vaccines.Collectively,we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity.Its manipulation could be used for the development of vaccines and adjuvants.

关键词： USP10 vaccines ubiquitin

Comparing T-and B-cell responses to COVID-19 vaccines across varied immune backgrounds

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3029-3038页

作者： Zhen Cui Wenxin Luo Ruihong Chen Yalun Li Zhoufeng Wang Yong Liu Shuo Liu LeiLei Feng Zijing Jia Ruixin Cheng Jun Tang Weijin Huang Yanjun Zhang Huawen Liu Xiangxi Wang Weimin Li CAS Key Laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China Department of Respiratory and Critical Care Medicine Institute of Respiratory HealthPrecision Medicine CenterPrecision Medicine Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu610041China Precision Medicine Center Precision Medicine Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu610041China Department of Neurology Chongqing University Three Gorges HospitalChongqing UniversityChongqingChina Division of HIV/AIDS and Sex-transmitted Virus vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)No.31 Huatuo StreetDaxing DistrictBeijing102629China Department of Microbiology Zhejiang Provincial Center for Disease Control and PreventionHangzhouChina Department of Oncology Chongqing University Three Gorges HospitalChongqing UniversityChongqingChina

The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide.A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages,while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells.However,specific T-cell responses remain largely unaffected by the mutations,indicating that T-cell-mediated cellular immunity can still provide protection.Moreover,the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo,which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1.These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies.The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health.The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants.Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.

关键词： vaccines immunity adapted

Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3806-3817页

作者： Yangzhuo Gu Jingyun Yang Cai He Tingmei Zhao Ran Lu Jian Liu Xianming Mo Fuqiang Wen Huashan Shi Department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China Division of Pulmonary Diseases State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China Laboratory of Stem Cell Biology and Department of Pediatric Surgery State Key Laboratory of BiotherapyWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including cancer and infectious diseases.Improvements of mRNA vaccines have been underway,among which boosting of efficacy is of great importance.Pam2Cys,a simple synthetic metabolizable lipoamino acid that signals through Toll-like receptor(TLR)2/6 pathway,eliciting both humoral and cellular adaptive immune responses,is an interesting candidate adjuvant.To investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys,the adjuvant was incorporated into mRNA-lipid nanoparticles(LNPs)to achieve co-delivery with mRNA.Immunization with the resulting mRNA-LNPs(Pam2Cys)shaped up the immune milieu in the draining lymph nodes(dLNs)through the induction of IL-12 and IL-17,among other cytokines.Antigen presentation was carried out mainly by migratory and dLNresident conventional type 2 DCs(cDC2s)and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4^(+) and CD8^(+) T cell-dependent fashion.Accompanying memory antitumor immunity was also established.Moreover,the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic model.Last but not the least,the new vaccines exhibited good preliminary safety profiles in murine models.These facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

关键词： vaccines immunity diseases

Viral vectored vaccines:design,development,preventive and therapeutic applications in human diseases

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2113-2150页

作者： Shen Wang Bo Liang Weiqi Wang Ling Li Na Feng Yongkun Zhao Tiecheng Wang Feihu Yan Songtao Yang Xianzhu Xia Key Laboratory of Jilin Province for Zoonosis Prevention and Control Changchun Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchunChina College of Veterinary Medicine Jilin UniversityChangchunChina China National Research Center for Exotic Animal Diseases China Animal Health and Epidemiology CenterQingdaoChina

Human diseases,particularly infectious diseases and cancers,pose unprecedented challenges to public health security and the global economy.The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease.Among all vaccine platforms,viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches.Currently,viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases.Numerous viruses of different families and origins,including vesicular stomatitis virus,rabies virus,parainfluenza virus,measles virus,Newcastle disease virus,influenza virus,adenovirus and poxvirus,are deemed to be prominent viral vectors that differ in structural characteristics,design strategy,antigen presentation capability,immunogenicity and protective efficacy.This review summarized the overall profile of the design strategies,progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines,simultaneously highlighting their potential for mucosal delivery,therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines.Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.

关键词： vaccines diseases protective