Genetic (DNA) Vaccines

With the development of various branches of medicine and biology the classical ideas about means to prevent infectious diseases have changed. Nowadays in different countries of the world, investigations are carried out intensively in the sphere of genetic vaccines. Distinctive feature of DNA-vaccination is long lasted expression in eukaryotic cell cytoplasm of nucleic acids encoding synthesis of immunogenic proteins. Genetic vaccines induce both humoral and cellular responses accompanied by production of large pool of immunological memory cells. A number of questions regarding features of gene-engineered construction and transfer of DNA-vaccines into the cells of macroorganism, structure of DNA-vaccines and mechanisms of immune response generation are considered in the review. Attention is paid on the safety of gene vaccination and ways to improve its efficiency.

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Coadministration of Gamma Interferon with DNA Vaccine Expressing Woodchuck Hepatitis Virus (WHV) Core Antigen Enhances the Specific Immune Response and Protects against WHV Infection

Journal of Virology ◽

10.1128/jvi.75.11.5036-5042.2001 ◽

2001 ◽

Vol 75 (11) ◽

pp. 5036-5042 ◽

Cited By ~ 30

Author(s):

Felix Siegel ◽

Mengji Lu ◽

Michael Roggendorf

Keyword(s):

Immune Response ◽

Immune Responses ◽

Dna Vaccines ◽

Hepatitis Virus ◽

Dna Vaccination ◽

Core Antigen ◽

Woodchuck Hepatitis Virus ◽

Lymphoproliferative Response ◽

Virus Challenge ◽

Cellular Immune

ABSTRACT DNA vaccinations are able to induce strong cellular immune responses in mice and confer protection against infectious agents. However, DNA vaccination of large animals appears to be less effective and requires repeated injections of large amounts of plasmid DNA. Enhancement of the efficiency of DNA vaccines may be achieved by coapplication of cytokine-expressing plasmids. Here we investigated, with woodchucks, whether coadministration of an expression plasmid for woodchuck gamma interferon (IFN-γ), pWIFN-γ, can improve DNA vaccination with woodchuck hepatitis virus core antigen (WHcAg). Animals were immunized with pWHcIm (a plasmid expressing WHcAg) alone or with a combination of pWHcIm and pWIFN-γ using a gene gun. Six weeks postimmunization, all animals were challenged with 105 genome equivalents of woodchuck hepatitis virus (WHV). The antibody and lymphoproliferative immune responses to WHV proteins were determined after immunization and after challenge. Vaccination with pWHcIm and pWIFN-γ led to a pronounced lymphoproliferative response to WHcAg and protected woodchucks against subsequent virus challenge. Two of three animals vaccinated with pWHcIm alone did not show a detectable lymphoproliferative response to WHcAg. A low-level WHV infection occurred in these woodchucks after challenge, as WHV DNA was detectable in the serum by PCR. None of the pWHcIm-vaccinated animals showed an anti-WHcAg antibody response after DNA vaccination or an anamnestic response after virus challenge. Our results indicate that coadministration of the WIFN-γ gene with pWHcIm enhanced the specific cellular immune response and improved the protective efficacy of WHV-specific DNA vaccines.

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Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from within

International Journal of Molecular Sciences ◽

10.3390/ijms22168523 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8523

Author(s):

Marta Luna-Sánchez ◽

Patrizia Bianchi ◽

Albert Quintana

Keyword(s):

Immune Response ◽

Genetic Material ◽

Mitochondrial Diseases ◽

Cellular Responses ◽

High Energy ◽

Eukaryotic Cell ◽

Mitochondrial Content ◽

Potential Therapeutic Target ◽

Cellular Immune ◽

Pro Inflammatory Cytokines

Symbiosis between the mitochondrion and the ancestor of the eukaryotic cell allowed cellular complexity and supported life. Mitochondria have specialized in many key functions ensuring cell homeostasis and survival. Thus, proper communication between mitochondria and cell nucleus is paramount for cellular health. However, due to their archaebacterial origin, mitochondria possess a high immunogenic potential. Indeed, mitochondria have been identified as an intracellular source of molecules that can elicit cellular responses to pathogens. Compromised mitochondrial integrity leads to release of mitochondrial content into the cytosol, which triggers an unwanted cellular immune response. Mitochondrial nucleic acids (mtDNA and mtRNA) can interact with the same cytoplasmic sensors that are specialized in recognizing genetic material from pathogens. High-energy demanding cells, such as neurons, are highly affected by deficits in mitochondrial function. Notably, mitochondrial dysfunction, neurodegeneration, and chronic inflammation are concurrent events in many severe debilitating disorders. Interestingly in this context of pathology, increasing number of studies have detected immune-activating mtDNA and mtRNA that induce an aberrant production of pro-inflammatory cytokines and interferon effectors. Thus, this review provides new insights on mitochondria-driven inflammation as a potential therapeutic target for neurodegenerative and primary mitochondrial diseases.

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Non-Lethal Sequential Individual Monitoring of Viremia in Relation to DNA Vaccination in Fish–Example Using a Salmon Alphavirus DNA Vaccine in Atlantic Salmon Salmo salar

Vaccines ◽

10.3390/vaccines9020163 ◽

2021 ◽

Vol 9 (2) ◽

pp. 163

Author(s):

Catherine Collins ◽

Katherine Lester ◽

Jorge Del-Pozo ◽

Bertrand Collet

Keyword(s):

Dna Vaccine ◽

Experimental Infection ◽

Vaccine Efficacy ◽

Dna Vaccines ◽

Experimental Studies ◽

Dna Vaccination ◽

Line System ◽

Individual Fish ◽

Antibody Levels ◽

Subtype 3

Traditionally, commercial testing for vaccine efficacy has relied on the mass infection of vaccinated and unvaccinated animals and the comparison of mortality prevalence and incidence. For some infection models where disease does not cause mortality this approach to testing vaccine efficacy is not useful. Additionally, in fish experimental studies on vaccine efficacy and immune response the norm is that several individuals are lethally sampled at sequential timepoints, and results are extrapolated to represent the kinetics of immune and disease parameters of an individual fish over the entire experimental infection period. In the present study we developed a new approach to vaccine testing for viremic viruses in fish by following the same individuals over the course of a DNA vaccination and experimental infection through repeated blood collection and analyses. Injectable DNA vaccines are particularly efficient against viral disease in fish. To date, two DNA vaccines have been authorised for use in fish farming, one in Canada against Infectious Haemorrhagic Necrotic virus and more recently one in Europe against Salmon Pancreatic Disease virus (SPDv) subtype 3. In the current study we engineered and used an experimental DNA vaccine against SPDv subtype 1. We measured viremia using a reporter cell line system and demonstrated that the viremia phase was completely extinguished following DNA vaccination. Differences in viremia infection kinetics between fish in the placebo group could be related to subsequent antibody levels in the individual fish, with higher antibody levels at terminal sampling in fish showing earlier viremia peaks. The results indicate that sequential non-lethal sampling can highlight associations between infection traits and immune responses measured at asynchronous timepoints and, can provide biological explanations for variation in data. Similar to results observed for the SPDv subtype 3 DNA vaccine, the SPDv subtype 1 DNA vaccine also induced an interferon type 1 response after vaccination and provided high protection against SPDv under laboratory conditions when fish were challenged at 7 weeks post-vaccination.

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Do fish erythrocytes have a potential role in the immune response orchestration after viral infection and DNA vaccination

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2013.03.111 ◽

2013 ◽

Vol 34 (6) ◽

pp. 1669-1670

Author(s):

M. Ortega-Villaizan ◽

A. Martínez-López ◽

P. García-Valtanen ◽

A.H. Teruel ◽

L. Perez ◽

...

Keyword(s):

Immune Response ◽

Viral Infection ◽

Potential Role ◽

Dna Vaccination

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A Report on COVID-19 Variants, COVID-19 Vaccines and the Impact of the Variants on the Efficacy of the Vaccines

Journal of Clinical and Medical Research ◽

10.37191/mapsci-2582-4333-3(3)-066 ◽

2021 ◽

Author(s):

Michael Halim

Keyword(s):

South Africa ◽

Immune Response ◽

Clinical Characteristics ◽

Systemic Review ◽

Review Of Literature ◽

Negative Effects ◽

Mortality And Morbidity ◽

The World ◽

Different Strains ◽

The Impact

The Coronavirus pandemic has caused negative effects across the globe; mortality and morbidity being the main impact. After WHO, termed the disease a pandemic in March 2020, they gave in health guidelines to follow to control the spread of the disease. The health industry, academia, and different governments are united to develop and test various vaccines at an unprecedented speed to combat the pandemic fully and bring the world back to its feet. Some of the vaccines developed include Pfizer, Moderna, and AstraZeneca. However, just like other viruses, the SAR-CoV-2 virus keeps changing through mutation, as various variants, different from the first one are emerging. Evidence shows that the three new variants; UK, Brazil, and South Africa are more severe in terms of transmissibility, disease severity, evading of the immune response, and reducing the ability to neutralized antibodies, compared to the original coronavirus. With such knowledge of the existence of different strains, the arises concerns on whether the already available vaccines are effective enough in preventing the new COVID-19 strains. Studies are still underdeveloped to learn more on the virologic, epidemiologic, and clinical characteristics of the ever-emerging variants. This research, through a systemic review of literature, seeks to find out whether the variants of SAR-CoV-2 have an impact on the efficacy of various vaccines developed in fighting the disease and the entire body’s immune response.

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Special Issue on "Immunomodulatory and therapeutic approaches against infectious diseases"

South Asian Journal of Experimental Biology ◽

10.38150/sajeb.1(5).p1-2 ◽

2011 ◽

Vol 1 (5) ◽

pp. 1-2

Author(s):

Lavkush Dwivedi

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Human Health ◽

Immune Stimulation ◽

Defense System ◽

Special Issue ◽

Therapeutic Approaches ◽

Major Constraint ◽

The World ◽

Insight Into

Infectious diseases and consequent immune imbalancesare major constraint in human health managementthroughout the world. However, in recentdecades enormous efforts have been made to elucidatethe immunomodulatory approaches againstinfectious diseases. Immunomodulation is a therapeuticapproach in which we try to intervene inauto regulating processes of the defense system toadjust the immune response at a desired level.The presentÃ‚Â special issue on cutting edge issues inImmunomodulation like Immune stimulation, Immunesuppression, Immune potentiating and immunereinforcement summarizes our current understandingof this complex mosaic. The accompanyingselection of recent articles from across theworld provides further insight into this topic.Â

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Design of genetic construction for creation DNA vaccine against porcine reproductive and respiratory syndrome

Proceedings of the National Academy of Sciences of Belarus Biological Series ◽

10.29235/1029-8940-2018-63-4-419-425 ◽

2018 ◽

Vol 63 (4) ◽

pp. 419-425

Author(s):

L. M. Kravchenko ◽

K. V. Kudzin ◽

U. A. Prakulevich

Keyword(s):

Immune Response ◽

Dna Vaccine ◽

Mammalian Cells ◽

Dna Vaccines ◽

Viral Vector ◽

Signal Sequence ◽

Regulatory Elements ◽

Economic Damage ◽

Chain Gene ◽

Prrs Virus

The porcine reproductive and respiratory syndrome (PRRS) caused the serious economic damage to swine breeding around the world. It is a viral infective disease against which live attenuated and inactivated vaccines are not always successful. Development of new types of drugs such as DNA vaccines is necessary for improving the protection against the virus. DNA vaccines induce the development of both a cellular and humoral immune response. Such vaccines consist of a plasmid or viral vector with genes of potentially immunogenic proteins. The expression of these genes realized in cells of the vaccinated animal. It leads to the synthesis of antigen proteins triggering the immune response. The purpose of this work is to create a genetic construction that can be used as DNA vaccine against PRRS virus. The construction consists of the commercial vector pVAX1 and open reading frame of two structural proteins of PRRS virus, a lysosomal localization signal sequence of the invariant chain gene and regulatory elements necessary for the expression of cloned genes in mammalian cells.

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How to Control Covid-19 with a Nanobiotherapy?

International Journal of Infectious Diseases and Research ◽

10.47485/2693-2326.1003 ◽

2020 ◽

Keyword(s):

Intensive Care Unit ◽

Immune Response ◽

Acute Respiratory Distress Syndrome ◽

Distress Syndrome ◽

Multiple Organ ◽

World Health ◽

Shortness Of Breath ◽

The World ◽

Health Organization ◽

Muscle Ache

The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. In a recent study of Nanshan Chen et al., on patients of Wuhan Jinyintan Hospital, Wuhan, China, from the 99 patients with SARSCoV-2 infection, 51% had chronic diseases and they had symptoms of fever (83%), cough (82%) shortness of breath (31%), muscle ache (11%), fatigue (9%), headache (8%), sore throat (5%), rhinorrhea (4%), chest pain (2%), diarrhea (2%), and nausea and vomiting (1%) [1, 2]. The majority of patients can recover, however, about 25% of patients will progress into severe complications including acute respiratory distress syndrome (ARDS), which may worsen rapidly into respiratory failure, need an intensive care unit (ICU) and even cause multiple organ failure [3]. Depending on the pathophysiological mechanisms supposed to be involved in the development of the various clinical forms of the disease, various types of treatment have been tested with varying degrees of success. We have developed a nanotherapy to block the entry of the virus into the host cell, to reduce its potential for replication and to regulate the immune response against the microbial aggressor [4].

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