Techniques for Developing and Assessing Immune Responses Induced by Synthetic DNA Vaccines for Emerging Infectious Diseases

2021 ◽  
pp. 229-263
Author(s):  
Ziyang Xu ◽  
Michelle Ho ◽  
Devivasha Bordoloi ◽  
Sagar Kudchodkar ◽  
Makan Khoshnejad ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Dna Vaccines ◽  
Emerging Infectious Diseases ◽  
Synthetic Dna

scholarly journals Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

2021 ◽  
Vol 18 (10) ◽  
pp. 2313-2324 ◽  
Author(s):  
Xin Wang ◽  
Gang Xu ◽  
Xiaoju Liu ◽  
Yang Liu ◽  
Shuye Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Severe Acute Respiratory Syndrome ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Single Cell ◽  
Emerging Infectious Diseases ◽  
Pathogenic Mechanisms ◽  
Host Immune Responses ◽  
Mechanistic Understanding

AbstractIn response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.

scholarly journals Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 382
Author(s):  
Jingjing Jiang ◽  
Stephanie J. Ramos ◽  
Preeti Bangalore ◽  
Dustin Elwood ◽  
Kathleen A. Cashman ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Vaccine Development ◽  
Dna Vaccines ◽  
Specific Binding ◽  
Emerging Infectious Diseases ◽  
Hemorrhagic Fever ◽  
Immune Memory ◽  
Global Public Health ◽  
Vaccine Platform

The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and nonhuman primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.

scholarly journals Multifaceted Functions of CH25H and 25HC to Modulate the Lipid Metabolism, Immune Responses, and Broadly Antiviral Activities

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 727 ◽  
Author(s):  
Jin Zhao ◽  
Jiaoshan Chen ◽  
Minchao Li ◽  
Musha Chen ◽  
Caijun Sun
Keyword(s):  
Lipid Metabolism ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Cholesterol Metabolism ◽  
Rift Valley Fever Virus ◽  
Antiviral Drug ◽  
Emerging Infectious Diseases ◽  
Cholesterol Homeostasis ◽  
Global Public Health ◽  
Antiviral Activities

With the frequent outbreaks of emerging infectious diseases in recent years, an effective broad-spectrum antiviral drug is becoming an urgent need for global public health. Cholesterol-25-hydroxylase (CH25H) and its enzymatic products 25-hydroxycholesterol (25HC), a well-known oxysterol that regulates lipid metabolism, have been reported to play multiple functions in modulating cholesterol homeostasis, inflammation, and immune responses. CH25H and 25HC were recently identified as exerting broadly antiviral activities, including upon a variety of highly pathogenic viruses such as human immunodeficiency virus (HIV), Ebola virus (EBOV), Nipah virus (NiV), Rift Valley fever virus (RVFV), and Zika virus (ZIKV). The underlying mechanisms for its antiviral activities are being extensively investigated but have not yet been fully clarified. In this study, we summarized the current findings on how CH25H and 25HC play multiple roles to modulate cholesterol metabolism, inflammation, immunity, and antiviral infections. Overall, 25HC should be further studied as a potential therapeutic agent to control emerging infectious diseases in the future.

scholarly journals A Proteome-Wide Immunoinformatics Tool to Accelerate T-Cell Epitope Discovery and Vaccine Design in the Context of Emerging Infectious Diseases: An Ethnicity-Oriented Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Patricio Oyarzun ◽  
Manju Kashyap ◽  
Victor Fica ◽  
Alexis Salas-Burgos ◽  
Faviel F. Gonzalez-Galarza ◽  
...  
Keyword(s):  
T Cell ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Cell Epitope ◽  
Emerging Infectious Diseases ◽  
Cd4 T Cell ◽  
Immune Responsiveness ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Epitope Discovery

Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics.

Sign in / Sign up

Export Citation Format

Share Document