Immune Response to Viral Vectors

1998 ◽  
pp. 147-157
Author(s):  
Jason G. Smith ◽  
Stephen L. Eck
Keyword(s):  
Immune Response ◽  
Viral Vectors

scholarly journals Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra J. Spencer ◽  
Paul F. McKay ◽  
Sandra Belij-Rammerstorfer ◽  
Marta Ulaszewska ◽  
Cameron D. Bissett ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cells ◽  
Immune Responses ◽  
Viral Vectors ◽  
Cytotoxic T Cells ◽  
Antibody Responses ◽  
Limited Data ◽  
Vectored Vaccine ◽  
Cellular Immune

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

scholarly journals Virus-Vectored Ebola Vaccines

Acta Naturae ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 4-11 ◽  
Author(s):  
I. V. Dolzhikova ◽  
E. A. Tokarskaya ◽  
A. S. Dzharullaeva ◽  
A. I. Tukhvatulin ◽  
D. V. Shcheblyakov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
West Africa ◽  
Protective Immunity ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Virus Disease ◽  
Genetically Engineered ◽  
Preclinical Trials

The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.

P24. Lack of Immune Response to Transgene-Encoded Protein After in Utero Injection of Adeno-Associated Viral Vectors

2008 ◽  
Vol 144 (2) ◽  
pp. 448
Author(s):  
Supriya S. Patel ◽  
Adrienne C. Dow ◽  
Ronald W. Busuttil ◽  
Gerald S. Lipshutz
Keyword(s):  
Immune Response ◽  
Viral Vectors ◽  
In Utero

Therapeutic Approaches for the Management of Autoimmune Disorders via Gene Therapy: Prospects, Challenges, and Opportunities

2021 ◽  
Vol 21 ◽  
Author(s):  
Rakesh K. Sindhu ◽  
Piyush Madaan ◽  
Parteek Chandel ◽  
Rokeya Akter ◽  
G. Adilakshmi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gene Therapy ◽  
Immune Response ◽  
Animal Models ◽  
Autoimmune Diseases ◽  
Animal Studies ◽  
Viral Vectors ◽  
Challenges And Opportunities ◽  
Organ Specific ◽  
Inflammatory Bowel

Background: Autoimmune diseases are the diseases that result due to the overactive immune response, and comprise systemic autoimmune diseases like rheumatoid arthritis (RA), sjӧgren’s syndrome (SS), and organ-specific autoimmune diseases like type-1 diabetes mellitus (T1DM), myasthenia gravis (MG), and inflammatory bowel disease (IBD). Currently, there is no long-term cure; but, several treatments exist which retard the evolution of the disease, embracing gene therapy, which has been scrutinized to hold immense aptitude for the management of autoimmune diseases. Objective: The review highlights the pathogenic mechanisms and genes liable for the development of autoimmune diseases, namely T1DM, type-2 diabetes mellitus (T2DM), RA, SS, IBD, and MG. Furthermore, the review focuses on investigating the outcomes of delivering the corrective genes with their specific viral vectors in various animal models experiencing these diseases to determine the effectiveness of gene therapy. Methods: Numerous review and research articles emphasizing the tremendous potential of gene therapy in the management of autoimmune diseases were procured from PubMed, MEDLINE, Frontier, and other databases and thoroughly studied for writing this review article. Results: The various animal models that experienced treatment with gene therapy have displayed regulation in the levels of proinflammatory cytokines, infiltration of lymphocytes, manifestations associated with autoimmune diseases, and maintained equilibrium in the immune response, thereby hinder the progression of autoimmune diseases. Conclusion: Gene therapy has revealed prodigious aptitude in the management of autoimmune diseases in various animal studies, but further investigation is essential to combat the limitations associated with it and before employing it on humans.

scholarly journals Multivalent and Multipathogen Viral Vector Vaccines

2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Katharina B. Lauer ◽  
Ray Borrow ◽  
Thomas J. Blanchard
Keyword(s):  
Immune Response ◽  
Measles Virus ◽  
Viral Vectors ◽  
Large Scale ◽  
Viral Vector ◽  
Natural Infection ◽  
Scale Production ◽  
Veterinary Vaccine ◽  
Large Scale Production ◽  
Foreign Proteins

ABSTRACT The presentation and delivery of antigens are crucial for inducing immunity and, desirably, lifelong protection. Recombinant viral vectors—proven safe and successful in veterinary vaccine applications—are ideal shuttles to deliver foreign proteins to induce an immune response with protective antibody levels by mimicking natural infection. Some examples of viral vectors are adenoviruses, measles virus, or poxviruses. The required attributes to qualify as a vaccine vector are as follows: stable insertion of coding sequences into the genome, induction of a protective immune response, a proven safety record, and the potential for large-scale production. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from the same or various pathogens. To protect effectively, some vaccines require multiple antigens of one pathogen or different pathogen serotypes/serogroups in combination (multivalent or polyvalent vaccines). Future multivalent vaccine candidates are likely to be required for complex diseases like malaria and HIV. Other novel strategies propose an antigen combination of different pathogens to protect against several diseases at once (multidisease or multipathogen vaccines).

scholarly journals Deciphering the Multifaceted Relationship between Oncolytic Viruses and Natural Killer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Christopher A. Alvarez-Breckenridge ◽  
Jianhua Yu ◽  
Balveen Kaur ◽  
Michael A. Caligiuri ◽  
E. Antonio Chiocca
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Viral Vectors ◽  
Nk Cell ◽  
Critical Factor ◽  
Oncolytic Viruses ◽  
Oncolytic Viral Therapy ◽  
Viral Therapy ◽  
Tumor Clearance ◽  
Active Research

Despite active research in virotherapy, this apparently safe modality has not achieved widespread success. The immune response to viral infection appears to be an essential factor that determines the efficacy of oncolytic viral therapy. The challenge is determining whether the viral-elicited immune response is a hindrance or a tool for viral treatment. NK cells are a key component of innate immunity that mediates antiviral immunity while also coordinating tumor clearance. Various reports have suggested that the NK response to oncolytic viral therapy is a critical factor in premature viral clearance while also mediating downstream antitumor immunity. As a result, particular attention should be given to the NK cell response to various oncolytic viral vectors and how their antiviral properties can be suppressed while maintaining tumor clearance. In this review we discuss the current literature on the NK response to oncolytic viral infection and how future studies clarify this intricate response.

scholarly journals Codon Usage and Adenovirus Fitness: Implications for Vaccine Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Judit Giménez-Roig ◽  
Estela Núñez-Manchón ◽  
Ramon Alemany ◽  
Eneko Villanueva ◽  
Cristina Fillat
Keyword(s):  
Immune Response ◽  
Codon Usage ◽  
Viral Vectors ◽  
Vaccine Development ◽  
Health Hazard ◽  
Recombinant Vaccines ◽  
Viral Epitope ◽  
Naturally Occurring ◽  
Cellular Immune ◽  
Viral Attenuation

Vaccination is the most effective method to date to prevent viral diseases. It intends to mimic a naturally occurring infection while avoiding the disease, exposing our bodies to viral antigens to trigger an immune response that will protect us from future infections. Among different strategies for vaccine development, recombinant vaccines are one of the most efficient ones. Recombinant vaccines use safe viral vectors as vehicles and incorporate a transgenic antigen of the pathogen against which we intend to generate an immune response. These vaccines can be based on replication-deficient viruses or replication-competent viruses. While the most effective strategy involves replication-competent viruses, they must be attenuated to prevent any health hazard while guaranteeing a strong humoral and cellular immune response. Several attenuation strategies for adenoviral-based vaccine development have been contemplated over time. In this paper, we will review them and discuss novel approaches based on the principle that protein synthesis from individual genes can be modulated by codon usage bias manipulation. We will summarize vaccine approaches that consider recoding of viral proteins to produce adenoviral attenuation and recoding of the transgene antigens for both viral attenuation and efficient viral epitope expression.

scholarly journals Immunization by replication-competent controlled herpesvirus vectors

2018 ◽  
Author(s):  
David C. Bloom ◽  
Robert K. Tran ◽  
Joyce Feller ◽  
Richard Voellmy
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Viral Vectors ◽  
T Cell Response ◽  
Equine Influenza Virus ◽  
Heterologous Antigen ◽  
Equine Influenza ◽  
Stringent Control ◽  
Gene Switch ◽  
Hsv 1

ABSTRACTReplication-competent controlled virus vectors were derived from virulent HSV-1 wildtype strain 17syn+ by placing one or two replication-essential genes under the stringent control of a gene switch that is co-activated by heat and an antiprogestin. Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy that approaches that of the wildtype virus from which they were derived. Essentially no replication occurs in the absence of activation. When administered to mice, localized application of a transient heat treatment in the presence of systemic antiprogestin results in efficient but limited virus replication at the site of administration. The immunogenicity of these viral vectors was tested in a mouse footpad lethal challenge model. Unactivated viral vectors - which may be regarded as equivalents of inactivated vaccines - induced detectable protection against lethality caused by wildtype virus challenge. Single activation of the viral vectors at the site of administration (rear footpads) greatly enhanced protective immune responses, and second immunization resulted in complete protection. Once activated vectors also induced far better neutralizing antibody and HSV-1-specific T cells responses than unactivated vectors. To find out whether the immunogenicity of a heterologous antigen was also enhanced in the context of efficient transient vector replication, a virus vector constitutively expressing an equine influenza virus hemagglutinin was constructed. Immunization of mice with this recombinant induced detectable antibody-mediated neutralization of equine influenza virus as well as a hemagglutinin-specific T cell response. Single activation of viral replication resulted in a several-fold enhancement of this immune response.IMPORTANCEWe hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, necessary safety should be provided by placing replication of the pathogen under stringent control and of activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above hypothesis as well as suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.

scholarly journals Molecular and Cellular Mechanisms of Antitumor Immune Response Activation by Dendritic Cells

Acta Naturae ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 17-30 ◽  
Author(s):  
O. V. Markov ◽  
N. L. Mironova ◽  
V. V. Vlasov ◽  
M. A. Zenkova
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Antigen Processing ◽  
Viral Vectors ◽  
Molecular Mechanisms ◽  
Antitumor Immune Response ◽  
Tumor Escape ◽  
Cellular Mechanisms ◽  
Cross Presentation ◽  
Cross Dressing

Dendritic cells (DCs) play a crucial role in the initiation and regulation of the antitumor immune response. Already , DC-based antitumor vaccines have been thoroughly explored both in animal tumor models and in clinical trials. DC-based vaccines are commonly produced from DC progenitors isolated from peripheral blood or bone marrow by culturing in the presence of cytokines, followed by loading the DCs with tumor-specific antigens, such as DNA, RNA, viral vectors, or a tumor cell lysate. However, the efficacy of DC-based vaccines remains low. Undoubtedly, a deeper understanding of the molecular mechanisms by which DCs function would allow us to enhance the antitumor efficacy of DC-based vaccines in clinical applications. This review describes the origin and major subsets of mouse and human DCs, as well as the differences between them. The cellular mechanisms of presentation and cross-presentation of exogenous antigens by DCs to T cells are described. We discuss intracellular antigen processing in DCs, cross-dressing, and the acquisition of the antigen cross-presentation function. A particular section in the review describes the mechanisms of tumor escape from immune surveillance through the suppression of DCs functions.

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