Malaria: pathology, immune response, and vaccine design: A mini review

Dengue infection is a global threat. As of today, there is no universal dengue fever treatment or vaccines unreservedly recommended by the World Health Organization. The investigation of the specific immune response to dengue virus would support antibody discovery as therapeutics for passive immunization and vaccine design. High-throughput sequencing enables the identification of the multitude of antibodies elicited in response to dengue infection at the sequence level. Artificial intelligence can mine the complex data generated and has the potential to uncover patterns in entire antibody repertoires and detect signatures distinctive of single virus-binding antibodies. However, these machine learning have not been harnessed to determine the immune response to dengue virus. In order to enable the application of machine learning, we have benchmarked existing methods for encoding biological and chemical knowledge as inputs and have investigated novel encoding techniques. We have applied different machine learning methods such as neural networks, random forests, and support vector machines and have investigated the parameter space to determine best performing algorithms for the detection and prediction of antibody patterns at the repertoire and antibody sequence levels in dengue-infected individuals. Our results show that immune response signatures to dengue are detectable both at the antibody repertoire and at the antibody sequence levels. By combining machine learning with phylogenies and network analysis, we generated novel sequences that present dengue-binding specific signatures. These results might aid further antibody discovery and support vaccine design.

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Hepatitis C virus vaccine design: focus on the humoral immune response

Journal of Biomedical Science ◽

10.1186/s12929-020-00669-4 ◽

2020 ◽

Vol 27 (1) ◽

Author(s):

Daniel Sepulveda-Crespo ◽

Salvador Resino ◽

Isidoro Martinez

Keyword(s):

Immune Response ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Vaccine ◽

Humoral Immune Response ◽

Vaccine Design ◽

Humoral Immune

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HLA-restricted immune response to mycobacterial antigens: relevance to vaccine design

Human Immunology ◽

10.1016/s0198-8859(99)00137-8 ◽

2000 ◽

Vol 61 (2) ◽

pp. 166-171 ◽

Cited By ~ 16

Author(s):

Abu Salim Mustafa

Keyword(s):

Immune Response ◽

Vaccine Design ◽

Mycobacterial Antigens

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Inflammatory and Autoimmune Reactions in Atherosclerosis and Vaccine Design Informatics

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/459798 ◽

2010 ◽

Vol 2010 ◽

pp. 1-16 ◽

Cited By ~ 7

Author(s):

Michael Jan ◽

Shu Meng ◽

Natalie C. Chen ◽

Jietang Mai ◽

Hong Wang ◽

...

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Vaccine Design ◽

Cardiovascular Morbidity ◽

Bioinformatic Tools ◽

High Affinity ◽

The Past ◽

Cardiovascular Morbidity And Mortality ◽

Active Research ◽

Positive Results

Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide. As its complex pathogenesis has been gradually unwoven, the regime of treatments and therapies has increased with still much ground to cover. Active research in the past decade has attempted to develop antiatherosclerosis vaccines with some positive results. Nevertheless, it remains to develop a vaccine against atherosclerosis with high affinity, specificity, efficiency, and minimal undesirable pathology. In this review, we explore vaccine development against atherosclerosis by interpolating a number of novel findings in the fields of vascular biology, immunology, and bioinformatics. With recent technological breakthroughs, vaccine development affords precision in specifying the nature of the desired immune response—useful when addressing a disease as complex as atherosclerosis with a manifold of inflammatory and autoimmune components. Moreover, our exploration of available bioinformatic tools for epitope-based vaccine design provides a method to avoid expenditure of excess time or resources.

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Guiding the Immune Response to a Conserved Epitope in MSP2, an Intrinsically Disordered Malaria Vaccine Candidate

Vaccines ◽

10.3390/vaccines9080855 ◽

2021 ◽

Vol 9 (8) ◽

pp. 855

Author(s):

Jeffrey Seow ◽

Sreedam C. Das ◽

Rodrigo A. V. Morales ◽

Ricardo Ataide ◽

Bankala Krishnarjuna ◽

...

Keyword(s):

Immune Response ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Single Point ◽

Peptide Vaccine ◽

Vaccine Design ◽

Single Point Mutation ◽

Strain Specificity ◽

Intrinsically Disordered ◽

Malaria Vaccine Candidate

The malaria vaccine candidate merozoite surface protein 2 (MSP2) has shown promise in clinical trials and is in part responsible for a reduction in parasite densities. However, strain-specific reductions in parasitaemia suggested that polymorphic regions of MSP2 are immuno-dominant. One strategy to bypass the hurdle of strain-specificity is to bias the immune response towards the conserved regions. Two mouse monoclonal antibodies, 4D11 and 9H4, recognise the conserved C-terminal region of MSP2. Although they bind overlapping epitopes, 4D11 reacts more strongly with native MSP2, suggesting that its epitope is more accessible on the parasite surface. In this study, a structure-based vaccine design approach was applied to the intrinsically disordered antigen, MSP2, using a crystal structure of 4D11 Fv in complex with its minimal binding epitope. Molecular dynamics simulations and surface plasmon resonance informed the design of a series of constrained peptides that mimicked the 4D11-bound epitope structure. These peptides were conjugated to keyhole limpet hemocyanin and used to immunise mice, with high to moderate antibody titres being generated in all groups. The specificities of antibody responses revealed that a single point mutation can focus the antibody response towards a more favourable epitope. This structure-based approach to peptide vaccine design may be useful not only for MSP2-based malaria vaccines, but also for other intrinsically disordered antigens.

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Molecular Mimicry of Carbohydrates by Peptides

Australian Journal of Chemistry ◽

10.1071/ch02047 ◽

2002 ◽

Vol 55 (2) ◽

pp. 13 ◽

Cited By ~ 30

Author(s):

M. A. Johnson ◽

B. M. Pinto

Keyword(s):

Immune Response ◽

Molecular Level ◽

Molecular Mimicry ◽

Vaccine Design ◽

Structural Data ◽

Alternative Source ◽

Mimetic Peptides ◽

The Subject

The use of carbohydrates as drugs and vaccines has several limitations. Molecular mimics of carbohydrates provide an alternative source of compounds to target pathways involving protein-carbohydrate interactions. In recent years, immunological studies have demonstrated the ability of certain peptides to act as molecular mimics of carbohydrates, in that they are able to induce an anti-carbohydrate immune response. Carbohydrate-mimetic peptides that bind to enzymes and lectins have also been discovered. The nature of this mimicry at the molecular level is currently the subject of investigation. Structural data regarding the origin of mimicry are reviewed, and their implications for drug and vaccine design are presented.

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