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 CRISPR/Cas System: A Potential Technology for the Prevention and Control of COVID-19 and Emerging Infectious Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Ronghua Ding ◽  
Jinzhao Long ◽  
Mingzhu Yuan ◽  
Yuefei Jin ◽  
Haiyan Yang ◽  
...  
Keyword(s):  
Public Health ◽  
Infectious Diseases ◽  
Prevention And Control ◽  
Pathogen Detection ◽  
Vaccine Development ◽  
Emerging Infectious Diseases ◽  
Public Health Problem ◽  
Global Public Health ◽  
The Future ◽  
And Control

The continued global pandemic of coronavirus disease 2019 (COVID-19) poses a serious threat to global public health and social stability and it has become a serious global public health problem. Unfortunately, existing diagnostic and therapeutic approaches for the prevention and control of COVID-19 have many shortcomings. In recent years, the emerging CRISPR/Cas technology can complement the problems of traditional methods. Biological tools based on CRISPR/Cas systems have been widely used in biomedicine. In particular, they are advantageous in pathogen detection, clinical antiviral therapy, drug, and vaccine development. Therefore, CRISPR/Cas technology may have great potential for application in the prevention and control of COVID-19 and emerging infectious diseases in the future. This article summarizes the existing applications of CRISPR/Cas technology in infectious diseases with the aim of providing effective strategies for the prevention and control of COVID-19 and other emerging infectious diseases in the future.

scholarly journals MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Vineet D. Menachery ◽  
Hugh D. Mitchell ◽  
Adam S. Cockrell ◽  
Lisa E. Gralinski ◽  
Boyd L. Yount ◽  
...  
Keyword(s):  
Public Health ◽  
Viral Replication ◽  
Rapid Response ◽  
Mutant Virus ◽  
Global Public Health ◽  
Vaccine Platform ◽  
Zoonotic Pathogens ◽  
Related Group

ABSTRACT While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward. IMPORTANCE The initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants. IMPORTANCE The initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.

scholarly journals A Novel Cre Recombinase-MediatedIn VivoMinicircle DNA (CRIM) Vaccine Provides Partial Protection against Newcastle Disease Virus

2019 ◽  
Vol 85 (14) ◽  
Author(s):  
Yanlong Jiang ◽  
Xing Gao ◽  
Ke Xu ◽  
Jianzhong Wang ◽  
Haibin Huang ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Vaccine Development ◽  
Cre Recombinase ◽  
Attractive Alternative ◽  
Vaccine Platform ◽  
Veterinary Vaccine ◽  
Minicircle Dna

ABSTRACTMinicircle DNA (mcDNA), which contains only the necessary components for eukaryotic expression and is thus smaller than traditional plasmids, has been designed for application in genetic manipulation. In this study, we constructed a novel plasmid containing both the Cre recombinase under the phosphoglycerate kinase (PGK) promoter and recombinantlox66andlox71sites located outside the cytomegalovirus (CMV) expression cassette. The strictly controlled synthesis of Cre recombinasein vivomaintained the complete form of the plasmidin vitro, whereas thein vivoproduction of Cre transformed the parental plasmid to mcDNA after transfection. The newly designedCrerecombinase-mediatedin vivomcDNA platform, named CRIM, significantly increased the nuclear entry of mcDNA, followed by increased production of mRNA and protein, using enhanced green fluorescent protein (EGFP) as a model. Similar results were also observed in chickens when the vaccine was delivered by the regulated-delayed-lysisSalmonellastrain χ11218, where significantly increased production of EGFP was observed in chicken livers. Then, we used the HN gene of genotype VII Newcastle disease virus as an antigen model to construct the traditional plasmid pYL43 and the novel mcDNA plasmid pYL47. After immunization, our CRIM vaccine provided significantly increased protection against challenge compared with that of the traditional plasmid, providing us with a novel mcDNA vaccine platform.IMPORTANCEMinicircle DNA (mcDNA) has been considered an attractive alternative to DNA vaccines; however, the relatively high cost and complicated process of purifying mcDNA dramatically restricts the application of mcDNA in the veterinary field. We designed a novelin vivomcDNA platform in which the complete plasmid could spontaneously transform into mcDNAin vivo. In combination with the regulated-delayed-lysisSalmonellastrain, the newly designed mcDNA vaccine provides us with an elegant platform for veterinary vaccine development.

scholarly journals Evaluation of the Impact of Codon Optimization and N-Linked Glycosylation on Functional Immunogenicity of Pfs25 DNA Vaccines Delivered byIn VivoElectroporation in Preclinical Studies in Mice

2015 ◽  
Vol 22 (9) ◽  
pp. 1013-1019 ◽  
Author(s):  
Dibyadyuti Datta ◽  
Geetha P. Bansal ◽  
Rajesh Kumar ◽  
Barry Ellefsen ◽  
Drew Hannaman ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Vaccine Development ◽  
Dna Vaccines ◽  
Codon Optimization ◽  
Antibody Responses ◽  
Transmission Blocking ◽  
Content Type ◽  
The Impact ◽  
Transmission Blocking Vaccine

ABSTRACTPlasmodium falciparumsexual stage surface antigen Pfs25 is a well-established candidate for malaria transmission-blocking vaccine development. Immunization with DNA vaccines encoding Pfs25 has been shown to elicit potent antibody responses in mice and nonhuman primates. Studies aimed at further optimization have revealed improved immunogenicity through the application ofin vivoelectroporation and by using a heterologous prime-boost approach. The goal of the studies reported here was to systematically evaluate the impact of codon optimization,in vivoelectroporation, and N-linked glycosylation on the immunogenicity of Pfs25 encoded by DNA vaccines. The results from this study demonstrate that while codon optimization andin vivoelectroporation greatly improved functional immunogenicity of Pfs25 DNA vaccines, the presence or absence of N-linked glycosylation did not significantly impact vaccine efficacy. These findings suggest that N-glycosylation of Pfs25 encoded by DNA vaccines is not detrimental to overall transmission-blocking efficacy.

scholarly journals Recent Advances in Vaccine Development for the Treatment of Emerging Infectious Diseases

2019 ◽  
Vol 53 (3) ◽  
pp. 343-354 ◽  
Author(s):  
Sahil Kumar ◽  
Kiran Thakur ◽  
Bandna Sharma ◽  
Tilak Raj Bhardwaj ◽  
Deo Nandan Prasad ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Vaccine Development ◽  
Emerging Infectious Diseases ◽  
Recent Advances

scholarly journals The impact of export regulations on recombinant viral vaccine development for emerging infectious diseases

Vaccine ◽  
2020 ◽  
Vol 38 (46) ◽  
pp. 7198-7200
Author(s):  
Jayanthi Wolf ◽  
Ryan Hansen ◽  
Kimberly Hassis ◽  
William Lapps ◽  
Emese Warmuth
Keyword(s):  
Infectious Diseases ◽  
Vaccine Development ◽  
Emerging Infectious Diseases ◽  
Viral Vaccine ◽  
The Impact

scholarly journals A bibliometric analysis of research on Ebola in Science Citation Index Expanded

2016 ◽  
Vol Volume 112 (Number 3/4) ◽  
Author(s):  
Anastassios Pouris ◽  
Yuh-Shan Ho ◽  
◽  
Keyword(s):  
Infectious Diseases ◽  
Ebola Virus ◽  
Emerging Infectious Diseases ◽  
The United States ◽  
World Health ◽  
Global Public Health ◽  
African Countries ◽  
Citation Pattern ◽  
Global Trends ◽  
Experimental Drugs

Abstract An unprecedented outbreak of the Ebola virus in 2014 claimed more than 1000 lives in West Africa and the World Health Organization declared a global public health emergency. This outbreak will undoubtedly promote additional research related to the Ebola virus and will create debate related to experimental drugs. This article identified the quantum of research in the field since 1991; the scientific disciplines that contributed to the field; the countries, organisations and authors that supported such research and the most cited articles. An increasing trend in annual production during 1991–2013 was observed. Journal of Virology, Journal of Infectious Diseases, and Virology were the three most productive journals in the field. Similarly, the field of virology dominated the 73 categories in which the Ebola research was classified. A total of 63 countries contributed to Ebola-related research, led by the USA. The most productive institutions were the United States Army Medical Research Institute of Infectious Diseases, the Centers for Disease Control and Prevention, and the National Institute of Allergy and Infectious Diseases. African countries were more likely to be involved in international collaboration than independent research. The most influential article exhibited a notable citation pattern and presented global trends in emerging infectious diseases.

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