scholarly journals Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Lassi Liljeroos ◽  
Enrico Malito ◽  
Ilaria Ferlenghi ◽  
Matthew James Bottomley
Keyword(s):  
Infectious Disease ◽  
Epitope Prediction ◽  
Protein Vaccine ◽  
Computational Approaches ◽  
Medical Interventions ◽  
Protective Antigens ◽  
Vaccine Antigens ◽  
Causative Agents ◽  
Potential Vaccine ◽  
Global Prevention

Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10–20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease.

scholarly journals Analysis of Known Bacterial Protein Vaccine Antigens Reveals Biased Physical Properties and Amino Acid Composition

2003 ◽  
Vol 4 (5) ◽  
pp. 468-478 ◽  
Author(s):  
Carl Mayers ◽  
Melanie Duffield ◽  
Sonya Rowe ◽  
Julie Miller ◽  
Bryan Lingard ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Pathogenic Bacteria ◽  
Vaccine Antigen ◽  
Bacterial Cells ◽  
Protein Vaccine ◽  
Vaccine Antigens ◽  
Candidate Protein ◽  
Potential Vaccine

Many vaccines have been developed from live attenuated forms of bacterial pathogens or from killed bacterial cells. However, an increased awareness of the potential for transient side-effects following vaccination has prompted an increased emphasis on the use of sub-unit vaccines, rather than those based on whole bacterial cells. The identification of vaccine sub-units is often a lengthy process and bioinformatics approaches have recently been used to identify candidate protein vaccine antigens. Such methods ultimately offer the promise of a more rapid advance towards preclinical studies with vaccines. We have compared the properties of known bacterial vaccine antigens against randomly selected proteins and identified differences in the make-up of these two groups. A computer algorithm that exploits these differences allows the identification of potential vaccine antigen candidates from pathogenic bacteria on the basis of their amino acid composition, a property inherently associated with sub-cellular location.

scholarly journals ReVac: a reverse vaccinology computational pipeline for prioritization of prokaryotic protein vaccine candidates

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Adonis D’Mello ◽  
Christian P. Ahearn ◽  
Timothy F. Murphy ◽  
Hervé Tettelin
Keyword(s):  
Machine Learning ◽  
Experimental Testing ◽  
Negative Control ◽  
Reverse Vaccinology ◽  
Learning Approaches ◽  
Protein Vaccine ◽  
Vaccine Candidates ◽  
Variable Expression ◽  
Prediction Tools ◽  
Potential Vaccine

Abstract Background Reverse vaccinology accelerates the discovery of potential vaccine candidates (PVCs) prior to experimental validation. Current programs typically use one bacterial proteome to identify PVCs through a filtering architecture using feature prediction programs or a machine learning approach. Filtering approaches may eliminate potential antigens based on limitations in the accuracy of prediction tools used. Machine learning approaches are heavily dependent on the selection of training datasets with experimentally validated antigens (positive control) and non-protective-antigens (negative control). The use of one or few bacterial proteomes does not assess PVC conservation among strains, an important feature of vaccine antigens. Results We present ReVac, which implements both a panoply of feature prediction programs without filtering out proteins, and scoring of candidates based on predictions made on curated positive and negative control PVCs datasets. ReVac surveys several genomes assessing protein conservation, as well as DNA and protein repeats, which may result in variable expression of PVCs. ReVac’s orthologous clustering of conserved genes, identifies core and dispensable genome components. This is useful for determining the degree of conservation of PVCs among the population of isolates for a given pathogen. Potential vaccine candidates are then prioritized based on conservation and overall feature-based scoring. We present the application of ReVac, applied to 69 Moraxella catarrhalis and 270 non-typeable Haemophilus influenzae genomes, prioritizing 64 and 29 proteins as PVCs, respectively. Conclusion ReVac’s use of a scoring scheme ranks PVCs for subsequent experimental testing. It employs a redundancy-based approach in its predictions of features using several prediction tools. The protein’s features are collated, and each protein is ranked based on the scoring scheme. Multi-genome analyses performed in ReVac allow for a comprehensive overview of PVCs from a pan-genome perspective, as an essential pre-requisite for any bacterial subunit vaccine design. ReVac prioritized PVCs of two human respiratory pathogens, identifying both novel and previously validated PVCs.

Surfaceome analysis of Australian epidemic Bordetella pertussis reveals potential vaccine antigens

Vaccine ◽  
2020 ◽  
Vol 38 (3) ◽  
pp. 539-548 ◽  
Author(s):  
Laurence Don Wai Luu ◽  
Sophie Octavia ◽  
Chelsea Aitken ◽  
Ling Zhong ◽  
Mark J. Raftery ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Vaccine Antigens ◽  
Potential Vaccine

scholarly journals Flagellin-F1-V Fusion Protein Is an Effective Plague Vaccine in Mice and Two Species of Nonhuman Primates

2008 ◽  
Vol 16 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Steven B. Mizel ◽  
Aaron H. Graff ◽  
Nammalwar Sriranganathan ◽  
Sean Ervin ◽  
Cynthia J. Lees ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Nonhuman Primates ◽  
High Yield ◽  
Protein Vaccine ◽  
Protective Antigens ◽  
Boost Immunization ◽  
Respiratory Challenge ◽  
Toll Like Receptor 5 ◽  
Substantial Change

ABSTRACT A number of studies have clearly demonstrated that flagellin is a potent adjuvant that promotes robust immune responses when it is given with a protein antigen. In view of the potential biological and practical benefits of a recombinant protein vaccine composed of a single fusion protein containing flagellin and antigen, we have evaluated the efficacy of a fusion protein composed of flagellin and two protective antigens of Yersinia pestis (F1 and V) in eliciting protection against respiratory challenge with Y. pestis. Flagellin-F1-V was produced and purified in high yield under good manufacturing practices conditions. The fusion protein retains full Toll-like receptor 5-stimulating activity in vitro. Using a prime-boost immunization protocol, we found that flagellin-F1-V elicits robust antigen-specific humoral immunity in mice and two species of nonhuman primates. Immune mice were fully protected against intranasal challenge with 150 mean tolerated doses of Y. pestis CO92. In immune mice, the bacteria were completely cleared within 3 days after challenge. Flagellin-F1-V exhibited full stability for at least 297 days at 4°C and at least 168 days at 25°C. At between 29 and 84 days at 37°C, the protein exhibited a loss of biological activity that appeared to be associated with a substantial change in protein diameter, possibly due to oligomerization. On the basis of our results, we believe that flagellin-F1-V is an outstanding candidate for evaluation in studies with humans.

scholarly journals Rickettsiosis as a critical emerging infectious disease in India

2017 ◽  
Vol 17 (4) ◽  
pp. 247-256
Author(s):  
K. Lalchhandama
Keyword(s):  
Infectious Disease ◽  
Scrub Typhus ◽  
Spotted Fever ◽  
Russian Far East ◽  
Far East ◽  
Historical Background ◽  
Indian States ◽  
The North ◽  
Causative Agents ◽  
Almost All

Gram-negative bacteria belonging to the order Rickettsiales such as Anaplasma, Ehrlichia, Neorickettsia, Rickettsia, and Orientia are the causative agents of infectious diseases collectively known as rickettsioses. Of the different rickettsial diseases, spotted fever and scrub typhus have ravaged India for the past couple of centuries. Specifically called the Indian tick typhus, spotted fever was discovered in India in the latter half of the 19th century. After several decades of dormancy, the disease re-emerged in several parts of India. Scrub typhus, originally discovered in Japan, has been recognised to be endemic to a so-called Tsutsugamushi Triangle, extending from Russian Far East and Korea in the north to northern Australia in the south and Afghanistan in the west, but the geographical description has now been breached. Not only in India, scrub typhus has emerged as the leading infectious disease in all endemic areas. Almost all Indian states have records of recurrent outbreaks. Infection can be of dire consequences, as multi-organ dysfunction and neurological disorder (meningocephalitis) are the common complications. This article discusses the historical background and scientific reports of rickettsioses in India.

scholarly journals Number of confirmed cases of viral hepatitis in Brazil between 2010 and 2015

2020 ◽  
pp. 71-80
Author(s):  
Filipe Sales Nunes ◽  
Lucas Facco ◽  
Amanda Alves Fecury ◽  
Maria Helena Mendonça de Araújo ◽  
Euzébio de Oliveira ◽  
...  
Keyword(s):  
Public Health ◽  
Infectious Disease ◽  
Viral Hepatitis ◽  
Laboratory Tests ◽  
Public Health Problem ◽  
Etiologic Agent ◽  
Molecular Test ◽  
Hepatitis Viruses ◽  
Causative Agents ◽  
Demand For Health

Viral hepatitis is an infectious disease that attacks the liver, and its causative agents are viruses. This work aims to demonstrate the number of confirmed cases of viral hepitis in Brazil between the years 2010 and 2015. A survey was carried out in the DATASUS database on the website (http://datasus.saude.gov. br /). Hepatitis represents a vast public health problem in Brazil. Of those infected, a large portion is composed of male individuals, with the visible lower demand for health services an important factor for this finding. Hepatitis B and C are the most common among viral hepatitis and one of the important factors that contribute to the rate of infection by the hepatitis viruses is their co-infection with HIV. Laboratory tests (immunoassay, molecular test) must be performed to detect markers and determine the etiologic agent that causes the pathology.

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