Immunogenicity of DNA Vaccines

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 7671

Special Issue Editor


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Guest Editor
Arboviruses, Rabies, Rickettsia and Related Zoonotic Diseases, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington St., Winnipeg, MB R3E 3R2, Canada
Interests: vaccine development; serological assay development; infection; immunology of infectious diseases; cell culture

Special Issue Information

Dear Colleagues,

Although DNA vaccines have been in development for more than 2 decades against a number of different diseases and ailments caused by pathogenic organisms, autoimmunity or cancer, there are still no approved DNA vaccines for human use, and the molecular and cellular processes that take place during this method to generate an effective immune response are not well understood. Early DNA vaccine technology saw good efficacy in small animals but experienced challenges in larger animals and humans to produce sufficient immunogenicity. To overcome these challenges, advancements in technology for DNA vaccine delivery introduced codon optimization for enhanced protein expression and saw the development of electroporation devices and formulations using lipid nanoparticles for improved transfection, revitalizing DNA vaccines as a viable candidate for humans. Recently, the ongoing SARS-CoV-2 pandemic has led to a number of labs specializing in DNA vaccines to exploit their technologies in both preclinical and clinical studies. According to the World Health Organization COVID-19 vaccine tracker and landscape, as of 26 November 2021, there are currently 16 DNA vaccines in preclinical development and 15 in various phases of clinical development against COVID-19, highlighting the quick response that DNA vaccine development can have during a crisis. Although the spotlight for COVID-19 has recently been on mRNA vaccines, DNA is easier to produce on a large scale, more stable than mRNA vaccines, and does not require injection in the muscle, making it a contender for vaccine delivery in areas of the world where logistical challenges pose a problem for other vaccines.

The goal of this Special Issue is to highlight our current understanding of the immunogenicity of DNA vaccines. We invite manuscripts that investigate the immune response elicited by DNA vaccines and the host response involved during DNA vaccination that may contribute to the development of better DNA vaccines with enhanced immunogenicity.

Dr. Alexander Bello
Guest Editor

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Keywords

  • DNA vaccine
  • immunogenicity
  • host response
  • molecular mechanisms
  • cellular mechanisms
  • innate immunity
  • adaptive immunity

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Published Papers (3 papers)

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Research

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18 pages, 6242 KiB  
Article
DNA Vaccine Co-Expressing Hemagglutinin and IFN-γ Provides Partial Protection to Ferrets against Lethal Challenge with Canine Distemper Virus
by Jianjun Zhao, Yiyang Sun, Ping Sui, Hongjun Pan, Yijun Shi, Jie Chen, Hailing Zhang, Xiaolong Wang, Rongshan Tao, Mengjia Liu, Dongbo Sun and Jiasan Zheng
Viruses 2023, 15(9), 1873; https://doi.org/10.3390/v15091873 - 4 Sep 2023
Cited by 1 | Viewed by 1191
Abstract
Canine distemper (CD), caused by canine distemper virus (CDV), is a highly contagious and lethal disease in domestic and wild carnivores. Although CDV live-attenuated vaccines have reduced the incidence of CD worldwide, low levels of protection are achieved in the presence of maternal [...] Read more.
Canine distemper (CD), caused by canine distemper virus (CDV), is a highly contagious and lethal disease in domestic and wild carnivores. Although CDV live-attenuated vaccines have reduced the incidence of CD worldwide, low levels of protection are achieved in the presence of maternal antibodies in juvenile animals. Moreover, live-attenuated CDV vaccines may retain residual virulence in highly susceptible species and cause disease. Here, we generated several CDV DNA vaccine candidates based on the biscistronic vector (pIRES) co-expressing virus wild-type or codon-optimized hemagglutinin (H) and nucleocapsid (N) or ferret interferon (IFN)-γ, as a molecular adjuvant, respectively. Apparently, ferret (Mustela putorius furo)-specific codon optimization increased the expression of CDV H and N proteins. A ferret model of CDV was used to evaluate the protective immune response of the DNA vaccines. The results of the vaccinated ferrets showed that the DNA vaccine co-expressing the genes of codon-optimized H and ferret IFN-γ (poptiH-IRES-IFN) elicited the highest anti-CDV serum-neutralizing antibodies titer (1:14) and cytokine responses (upregulated TNF-α, IL-4, IL-2, and IFN-γ expression) after the third immunization. Following vaccination, the animals were challenged with a lethal CDV 5804Pe/H strain with a dose of 105.0 TCID50. Protective immune responses induced by the DNA vaccine alleviated clinical symptoms and pathological changes in CDV-infected ferrets. However, it cannot completely prevent virus replication and viremia in vivo as well as virus shedding due to the limited neutralizing antibody level, which eventually contributed to a survival rate of 75% (3/4) against CDV infection. Therefore, the improved strategies for the present DNA vaccines should be taken into consideration to develop more protective immunity, which includes increasing antigen expression or alternative delivery routes, such as gene gun injection. Full article
(This article belongs to the Special Issue Immunogenicity of DNA Vaccines)
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10 pages, 1972 KiB  
Article
Development of DNA Vaccine Candidate against SARS-CoV-2
by Xingyun Wang, Nino Rcheulishvili, Jie Cai, Cong Liu, Fengfei Xie, Xing Hu, Nuo Yang, Mengqi Hou, Dimitri Papukashvili, Yunjiao He and Peng George Wang
Viruses 2022, 14(5), 1049; https://doi.org/10.3390/v14051049 - 15 May 2022
Cited by 7 | Viewed by 3781
Abstract
Despite the existence of various types of vaccines and the involvement of the world’s leading pharmaceutical companies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the most challenging health threat in this century. Along with the increased transmissibility, new strains continue to emerge [...] Read more.
Despite the existence of various types of vaccines and the involvement of the world’s leading pharmaceutical companies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the most challenging health threat in this century. Along with the increased transmissibility, new strains continue to emerge leading to the need for more vaccines that would elicit protectiveness and safety against the new strains of the virus. Nucleic acid vaccines seem to be the most effective approach in case of a sudden outbreak of infection or the emergence of a new strain as it requires less time than any conventional vaccine development. Hence, in the current study, a DNA vaccine encoding the trimeric prefusion-stabilized ectodomain (S1+S2) of SARS-CoV-2 S-protein was designed by introducing six additional prolines mutation, termed HexaPro. The three-dose regimen of designed DNA vaccine immunization in mice demonstrated the generation of protective antibodies. Full article
(This article belongs to the Special Issue Immunogenicity of DNA Vaccines)
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Review

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21 pages, 997 KiB  
Review
Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses
by Peter Pushko, Igor S. Lukashevich, Dylan M. Johnson and Irina Tretyakova
Viruses 2024, 16(3), 428; https://doi.org/10.3390/v16030428 - 10 Mar 2024
Cited by 1 | Viewed by 1996
Abstract
Single-dose, immunogenic DNA (iDNA) vaccines coding for whole live-attenuated viruses are reviewed. This platform, sometimes called immunization DNA, has been used for vaccine development for flavi- and alphaviruses. An iDNA vaccine uses plasmid DNA to launch live-attenuated virus vaccines in vitro or in [...] Read more.
Single-dose, immunogenic DNA (iDNA) vaccines coding for whole live-attenuated viruses are reviewed. This platform, sometimes called immunization DNA, has been used for vaccine development for flavi- and alphaviruses. An iDNA vaccine uses plasmid DNA to launch live-attenuated virus vaccines in vitro or in vivo. When iDNA is injected into mammalian cells in vitro or in vivo, the RNA genome of an attenuated virus is transcribed, which starts replication of a defined, live-attenuated vaccine virus in cell culture or the cells of a vaccine recipient. In the latter case, an immune response to the live virus vaccine is elicited, which protects against the pathogenic virus. Unlike other nucleic acid vaccines, such as mRNA and standard DNA vaccines, iDNA vaccines elicit protection with a single dose, thus providing major improvement to epidemic preparedness. Still, iDNA vaccines retain the advantages of other nucleic acid vaccines. In summary, the iDNA platform combines the advantages of reverse genetics and DNA immunization with the high immunogenicity of live-attenuated vaccines, resulting in enhanced safety and immunogenicity. This vaccine platform has expanded the field of genetic DNA and RNA vaccines with a novel type of immunogenic DNA vaccines that encode entire live-attenuated viruses. Full article
(This article belongs to the Special Issue Immunogenicity of DNA Vaccines)
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