Biotechnology and vaccines: application of functional genomics to Neisseria meningitidis and other bacterial pathogens

Since its introduction, vaccinology has been very effective in preventing infectious diseases. However, in several cases, the conventional approach to identify protective antigens, based on biochemical, immunological and microbiological methods, has failed to deliver successful vaccine candidates against major bacterial pathogens. The recent development of powerful biotechnological tools applied to genome-based approaches has revolutionized vaccine development, biological research and clinical diagnostics. The availability of a genome provides an inclusive virtual catalogue of all the potential antigens from which it is possible to select the molecules that are likely to be more effective. Here, we describe the use of "reverse vaccinology", which has been successful in the identification of potential vaccines candidates against Neisseria meningitidis serogroup B and review the use of functional genomics approaches as DNA microarrays, proteomics and comparative genome analysis for the identification of virulence factors and novel vaccine candidates. In addition, we describe the potential of these powerful technologies in understanding the pathogenesis of various bacteria.     

Antibacterial vaccine design using genomics and proteomics

After 200 years of practice, vaccinology has proved to be very effective in preventing infectious diseases. However, several human and animal pathogens exist for which vaccines have not yet been discovered. As for other fields of medical sciences, it is expected that vaccinology will greatly benefit from the emerging genomics technologies such as bioinformatics, proteomics and DNA microarrays. In this article the potential of these technologies applied to bacterial pathogens is analyzed, taking into account the few existing examples of their application in vaccine discovery.     

Cell biology, chemogenomics and chemoproteomics

The scientific techniques used in molecular biological research and drug discovery have changed dramatically over the past 10 years due to the influence of genomics, proteomics and bioinformatics. Furthermore, genomics and functional genomics are now merging into a new scientific approach called chemogenomics. Advancements in the study of molecular cell biology are dependent upon "omics" researchers realizing the importance of and using the experimental tools currently available to cell biologists. For example, novel microscopic techniques utilizing advanced computer imaging allow for the examination of live specimens in a fourth dimension, viz., time. Yet, molecular biologists have not taken full advantage of these and other traditional and novel cell biology techniques for the further advancement of genomic and proteomic-oriented research. The application of traditional and novel cellular biological techniques will enhance the science of genomics. The authors hypothesize that a stronger interdisciplinary approach must be taken between cell biology (and its closely related fields) and genomics, proteomics and bio-chemoinformatics. Since there is a lot of confusion regarding many of the "omics" definitions, this article also clarifies some of the basic terminology used in genomics, and related fields. It also reviews the current status and future potential of chemogenomics and its relationship to cell biology. The authors also discuss and expand upon the differences between chemogenomics and the relatively new term--chemoproteomics. We conclude that the advances in cell biology methods and approaches and their adoption by "omics" researchers will allow scientists to maximize our knowledge about life.     

Helicobacter pylori vaccine development based on combined subproteome analysis

Effective vaccines could provide long-term solutions to many important infectious diseases, however, vaccine development has been hampered by the slow identification of protective antigens. Proteomics provides global information about relevant antigen properties and thus might be ideally suited for identifying promising vaccine antigen subsets. Helicobacter pylori proteomics data are stored in a proteomics database (http://www.mpiib-berlin.mpg.de/2D-PAGE/). In this review, we describe how a combined Helicobacter subproteome analysis resulted in the rapid identification of novel, highly protective antigens. This illustrates the great potential of pathogen proteomics for vaccine development.     

Omics tools enabling vaccine discovery against fasciolosis

In the past decade significant advances in our understanding of liver fluke biology have been made through in-depth interrogation and analysis of evolving Fasciola hepatica and Fasciola gigantica omics datasets. This information is crucial for developing novel control strategies, particularly vaccines necessitated by the global spread of anthelmintic resistance. Distilling them down to a manageable number of testable vaccines requires combined rational, empirical, and collaborative approaches. Despite a lack of clear outstanding vaccine candidate(s), we must continue to identify salient parasite–host interacting molecules, likely in the secretory products, tegument, or extracellular vesicles, and perform robust trials especially in livestock, using present and emerging vaccinology technologies to discover that elusive liver fluke vaccine. Omics tools are bringing this prospect ever closer.     

The top five "game changers" in vaccinology: toward rational and directed vaccine development

Despite the tremendous success of the classical "isolate, inactivate, and inject" approach to vaccine development, new breakthroughs in vaccine research are increasingly reliant on novel approaches that incorporate cutting edge technology and advances in innate and adaptive immunology, microbiology, virology, pathogen biology, genetics, bioinformatics, and many other disciplines in order to: (1) deepen our understanding of the key biological processes that lead to protective immunity, (2) observe vaccine responses on a global, systems level, and (3) directly apply the new knowledge gained to the development of next-generation vaccines with improved safety profiles, enhanced efficacy, and even targeted utility in select populations. Here we highlight five key components foundational to vaccinomics efforts: applied immunogenomics, next generation sequencing and other cutting-edge "omics" technologies, advanced bioinformatics and analysis techniques, and finally, systems biology applied to immune profiling and vaccine responses. We believe these "game changers" will play a critical role in moving us toward the rational and directed development of new vaccines in the 21st century.     

Proteomics for development of vaccine

The success of genome projects has provided us with a vast amount of information on genes of many pathogenic species and has raised hopes for rapid progress in combating infectious diseases, both by construction of new effective vaccines and by creating a new generation of therapeutic drugs. Proteomics, a strategy complementary to the genomic-based approach, when combined with immunomics (looking for immunogenic proteins) and vaccinomics (characterization of host response to immunization), delivers valuable information on pathogen-host cell interaction. It also speeds the identification and detailed characterization of new antigens, which are potential candidates for vaccine development. This review begins with an overview of the global status of vaccinology based on WHO data. The main part of this review describes the impact of proteomic strategies on advancements in constructing effective antibacterial, antiviral and anticancer vaccines. Diverse aspects of disease mechanisms and disease preventions have been investigated by proteomics.     

组学技术在产油微生物中的应用

微生物油脂是未来燃料和食品用油的重要潜在资源。近年来,随着系统生物学技术的快速发展,从全局角度理解产油微生物生理代谢及脂质积累的特征成为研究热点。组学技术作为系统生物学研究的重要工具被广泛用于揭示产油微生物脂质高效生产的机制研究中,这为产油微生物理性遗传改造和发酵过程控制提供了基础。文中对组学技术在产油微生物中的应用概况进行了综述,介绍了产油微生物组学分析常用的样品前处理及数据分析方法,综述了包括基因组、转录组、蛋白(修饰)组及代谢(脂质)组等在内的多种组学技术,以及组学数据基础上的数学模型在揭示产油微生物脂质高效生产机制中的研究,并对未来发展和应用进行了展望。     

Strategies for successful designing of immunocontraceptive vaccines and recent updates in vaccine development against sexually transmitted infections - A review

BackgroundThe world population is continuously growing. It has been estimated that half of the world’s population is from the Asian continent, mainly from China and India. Overpopulation may lead to many societal problems as well as to changes in the habitat. Birth control measures are thus needed to control this growth. However, for the last 50–60 years, there have not been any improvements in the field of contraception. Nevertheless, the immunocontraceptive vaccine is an emerging field, and it might be the only replacement for the existing mode of contraception for the next millennium. Sexually transmitted infections (STIs) are frequent, and their transmission rate increases yearly. As antibiotics are the prevailing treatment for this kind of infections, resistance in humans has increased; therefore, having effective antibiotic treatments for STIs is now a concern. Vaccines against STIs are now needed. It is thought that the improvements in the fields of proteomics, immunomics, metabolomics, and other omics will help in the successful development of vaccines.ObjectiveTo collect and review the literature about recent advancements in immunocontraception and vaccines against sexually transmitted diseases/infections.MethodsReliable scientific databases, such as PubMed Central, PubMed, Scopus, Science Direct, and Goggle Scholar, were consulted. Publications bearing important information on targeted antigens/immunogens for contraceptive vaccine design and advancements in vaccine development for STIs were gathered and tabulated, and details were analyzed as per the theme of each study.ResultsImportant antigens that have a specific role in fertility have been studied extensively for their contraceptive nature. Additionally, the advancements in the screening for the best antigens, according to their antigenic nature and how they elicit immune responses for an extended period were also studied. Herd immunity for STIs and advancements in the development of vaccines for syphilis, gonorrhea, and herpes simplex virus were also studied and tabulated in this review. An extensive knowledge on STIs vaccines was gained.ConclusionThis extensive review is aimed to provide insights for active researchers in vaccinology, immunology, and reproductive biology. Advancements in the development of vaccines for different STIs can be gathered as a wholesome report.     

Pathogen proteins eliciting antibodies do not share epitopes with host proteins: a bioinformatics approach

The best way to prevent diseases caused by pathogens is by the use of vaccines. The advent of genomics enables genome-wide searches of new vaccine candidates, called reverse vaccinology. The most common strategy to apply reverse vaccinology is by designing subunit recombinant vaccines, which usually generate an humoral immune response due to B-cell epitopes in proteins. A major problem for this strategy is the identification of protective immunogenic proteins from the surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena related to several human diseases. A sequence-based computational analysis has been carried out applying the BLASTP algorithm. Therefore, two huge databases have been created, one with the most complete and current linear B-cell epitopes, and the other one with the surface-protein sequences of the main human respiratory bacterial pathogens. We found that none of the 7353 linear B-cell epitopes analysed shares any sequence identity region with human proteins capable of generating antibodies, and that only 1% of the 2175 exposed proteins analysed contain a stretch of shared sequence with the human proteome. These findings suggest the existence of a mechanism to avoid autoimmunity. We also propose a strategy for corroborating or warning about the viability of a protein linear B-cell epitope as a putative vaccine candidate in a reverse vaccinology study; so, epitopes without any sequence identity with human proteins should be very good vaccine candidates, and the other way around.     

关于组学大数据背景下《微生物学》教材框架的思考

微生物学是生物学的重要内容,是全国高等院校生物学专业或相关专业的本科生必修的一门核心基础课,其主要任务是给学生提供基础的、系统的、前沿的微生物学知识和理论。随着高通量测序、质谱、芯片等高通量技术的快速发展,生命科学领域快速进入了以海量多元组学(基因组学、转录组学、蛋白质组学、免疫组学、代谢组学等)数据为特征的大数据时代,而这势必会对微生物学教材已有的内容产生冲击和补充。本文对如何在组学大数据背景下对国内经典的微生物学教材进行改革,将目前最具突破性的组学成果整合到已有的教材框架中或革新现有教材框架进行了初步探讨。     

保护性病毒抗原的筛选策略及其在新型疫苗研发中的应用

随着疫苗研发技术的发展,新型疫苗在传染病的预防中得到了广泛应用。由于新型疫苗安全性良好,因此其在烈性病疫苗的应用中有着得天独厚的优势,然而研制新型疫苗的前提是筛选出保护性抗原。随着各种组学研究的发展,针对真核生物的多种生物信息学方法代表着最前沿的技术手段。相对于真核细胞,病毒具有更为简单的结构,对应着相对简单的研究方法,未来的保护性抗原筛选策略,需要结合生物信息学和传统分子生物学方法的优势。本文分别从宿主和病毒入手,论述了病毒保护性抗原的筛选策略,列举了一系列基于真核细胞开发的可能用于保护性抗原筛选的生物信息学方法,并总结了应用保护性抗原进行新型疫苗设计的案例,以便加深对病毒保护性抗原筛选策略的认知,为新型疫苗的研发提供借鉴。     

Historical Advances in Structural and Molecular Biology and How They Impacted Vaccine Development

Vaccines are among the greatest tools for prevention and control of disease. They have eliminated smallpox from the planet, decreased morbidity and mortality for major infectious diseases like polio, measles, mumps, and rubella, significantly blunted the impact of the COVID-19 pandemic, and prevented viral induced cancers such as cervical cancer caused by human papillomavirus. Recent technological advances, in genomics, structural biology, and human immunology have transformed vaccine development, enabling new technologies such as mRNA vaccines to greatly accelerate development of new and improved vaccines. In this review, we briefly highlight the history of vaccine development, and provide examples of where advances in genomics and structural biology, paved the way for development of vaccines for bacterial and viral diseases.     

多组学技术及其在生命科学研究中应用概述

随着新一代测序技术、高分辨质谱技术、多组学整合分析方法及数据库的发展,组学技术正从传统的单一组学向多组学技术发展。以多组学驱动的系统生物学研究将带来生命科学研究的新范式。本文简要概述了基因组学、表观基因组学、转录组学,蛋白质组学及代谢组学的进展,重点介绍多组学技术平台的组成和功能,多组学技术的应用现状及在合成生物学及生物医学等领域的应用前景。