scholarly journals Self-Replicating RNA Viruses for Vaccine Development Against Infectious Diseases and Cancer

2021 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Measles Virus ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Vaccine Candidates ◽  
Vector Systems

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

scholarly journals Self-Amplifying RNA Viruses as RNA Vaccines

2020 ◽  
Vol 21 (14) ◽  
pp. 5130 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Tumor Antigens ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Emerging Diseases ◽  
Host Cells ◽  
Phase Iii ◽  
Rna Replicon

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases.

scholarly journals Self-Replicating RNA Viruses for Vaccine Development against Infectious Diseases and Cancer

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1187
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Infectious Diseases ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Tumor Antigens ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Virus Disease ◽  
Recombinant Protein Expression ◽  
Polymerase Activity ◽  
Surface Proteins

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered for recombinant protein expression and vaccine development. Due to the presence of RNA-dependent RNA polymerase activity, subgenomic RNA can replicate close to 106 copies per cell for translation in the cytoplasm providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. Self-replicating RNA viral vectors can be administered as replicon RNA at significantly lower doses than conventional mRNA, recombinant particles, or DNA plasmids. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus, etc., showing robust immune response and protection in animal models. Recently, paramyxovirus and rhabdovirus vector-based SARS-CoV-2 vaccines as well as RNA vaccines based on self-amplifying alphaviruses have been evaluated in clinical settings. Vaccines against various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been developed. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

scholarly journals Viral vector-based vaccines against SARS-CoV-2

2021 ◽  
pp. 295-308
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Measles Virus ◽  
Viral Vectors ◽  
Vaccine Development ◽  
Viral Vector ◽  
Adenovirus Vector ◽  
Influenza Viruses ◽  
Vaccine Candidates ◽  
Lentivirus Vectors

Viral vectors have been frequently applied for vaccine development. It has also been the case for vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to tackle the coronavirus disease 2019 (COVID-19) pandemic. A multitude of different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as antigen. Intramuscular injection has been most commonly used, but also intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced with several vaccines receiving Emergency Use Authorization (EUA). The simian ChAdOx1 nCoV-19 vaccine applied as a prime-boost regimen has provided 62.1–90% vaccine efficacy in clinical trials. The Ad26.COV2.S vaccine requires only one immunization to provide protection against SARS-CoV-2. The rAd26-S/rAd5-S vaccine utilizes the Ad26 serotype for the prime immunization followed by a boost with the Ad5 serotype resulting in 91.2% vaccine efficacy. All adenovirus-based vaccines are used for mass vaccinations. Moreover, vaccine candidates based on vaccinia virus and lentivirus vectors have been subjected to clinical evaluation. Among self-replicating RNA viruses, vaccine vectors based on measles virus, rhabdoviruses, and alphaviruses have been engineered and tested in clinical trials. In addition to the intramuscular route of administration vaccine candidates based on influenza viruses and adenoviruses have been subjected to intranasal delivery showing antibody responses and protection against SARS-CoV-2 challenges in animal models. The detection of novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs to be monitored. Moreover, the cause of recently documented rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) must be investigated.

scholarly journals Self-Replicating RNA Viruses for RNA Therapeutics

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3310 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Antibody Responses ◽  
Phase Iii ◽  
Phase I Clinical Trials

Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.

scholarly journals Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Rajashri Bezbaruah ◽  
Pobitra Borah ◽  
Bibhuti Bhushan Kakoti ◽  
Nizar A. Al-Shar’I ◽  
Balakumar Chandrasekaran ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Viral Vector ◽  
World Health ◽  
Prolonged Incubation ◽  
Vaccine Candidates ◽  
Vector Vaccine ◽  
Dna And Rna ◽  
Viral Vector Vaccine

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19.

scholarly journals Sex Differences in Immunity: Implications for the Development of Novel Vaccines Against Emerging Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Anahita Fathi ◽  
Marylyn M. Addo ◽  
Christine Dahlke
Keyword(s):  
Clinical Trials ◽  
Sex Differences ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Virus Disease ◽  
Emerging Infectious Diseases ◽  
Vaccine Safety ◽  
Emerging Infections ◽  
Emerging Pathogens ◽  
Vaccine Candidates

Vaccines are one of the greatest public health achievements and have saved millions of lives. They represent a key countermeasure to limit epidemics caused by emerging infectious diseases. The Ebola virus disease crisis in West Africa dramatically revealed the need for a rapid and strategic development of vaccines to effectively control outbreaks. Seven years later, in light of the SARS-CoV-2 pandemic, this need has never been as urgent as it is today. Vaccine development and implementation of clinical trials have been greatly accelerated, but still lack strategic design and evaluation. Responses to vaccination can vary widely across individuals based on factors like age, microbiome, co-morbidities and sex. The latter aspect has received more and more attention in recent years and a growing body of data provide evidence that sex-specific effects may lead to different outcomes of vaccine safety and efficacy. As these differences might have a significant impact on the resulting optimal vaccine regimen, sex-based differences should already be considered and investigated in pre-clinical and clinical trials. In this Review, we will highlight the clinical observations of sex-specific differences in response to vaccination, delineate sex differences in immune mechanisms, and will discuss the possible resulting implications for development of vaccine candidates against emerging infections. As multiple vaccine candidates against COVID-19 that target the same antigen are tested, vaccine development may undergo a decisive change, since we now have the opportunity to better understand mechanisms that influence vaccine-induced reactogenicity and effectiveness of different vaccines.

scholarly journals RNA Viruses as Tools in Gene Therapy and Vaccine Development

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 189 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Viral Vectors ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Tumor Regression ◽  
Rna Virus ◽  
Progression Free Survival ◽  
Prolonged Survival ◽  
Expression Vectors

RNA viruses have been subjected to substantial engineering efforts to support gene therapy applications and vaccine development. Typically, retroviruses, lentiviruses, alphaviruses, flaviviruses rhabdoviruses, measles viruses, Newcastle disease viruses, and picornaviruses have been employed as expression vectors for treatment of various diseases including different types of cancers, hemophilia, and infectious diseases. Moreover, vaccination with viral vectors has evaluated immunogenicity against infectious agents and protection against challenges with pathogenic organisms. Several preclinical studies in animal models have confirmed both immune responses and protection against lethal challenges. Similarly, administration of RNA viral vectors in animals implanted with tumor xenografts resulted in tumor regression and prolonged survival, and in some cases complete tumor clearance. Based on preclinical results, clinical trials have been conducted to establish the safety of RNA virus delivery. Moreover, stem cell-based lentiviral therapy provided life-long production of factor VIII potentially generating a cure for hemophilia A. Several clinical trials on cancer patients have generated anti-tumor activity, prolonged survival, and even progression-free survival.

scholarly journals The Rise of Vectored Vaccines: A Legacy of the COVID-19 Global Crisis

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1101
Author(s):  
Danielle Soares de Oliveira Daian e Silva ◽  
Flávio Guimarães da Fonseca
Keyword(s):  
Clinical Trials ◽  
Influenza Virus ◽  
Immune Responses ◽  
Research And Development ◽  
Measles Virus ◽  
Viral Vectors ◽  
Vaccine Research ◽  
Global Context ◽  
The World ◽  
New Vaccines

The COVID-19 pandemic represents a milestone in vaccine research and development in a global context. A worldwide effort, as never seen before, involved scientists from all over the world in favor of the fast, accurate and precise construction and testing of immunogens against the new coronavirus, SARS-CoV-2. Among all the vaccine strategies put into play for study and validation, those based on recombinant viral vectors gained special attention due to their effectiveness, ease of production and the amplitude of the triggered immune responses. Some of these new vaccines have already been approved for emergency/full use, while others are still in pre- and clinical trials. In this article we will highlight what is behind adeno-associated vectors, such as those presented by the immunogens ChaAdOx1, Sputnik, Convidecia (CanSino, Tianjin, China), and Janssen (Johnson & Johnson, New Jersey, EUA), in addition to other promising platforms such as Vaccinia virus MVA, influenza virus, and measles virus, among others.

scholarly journals Services Marketing of COVID-19 Vaccines in the Present Scenario

2020 ◽  
Vol 6 (11) ◽  
pp. 143-146
Author(s):  
Dr. Rachana Nagar Dr. Naveen Sharma and Garima Sharma
Keyword(s):  
Clinical Trials ◽  
Infectious Diseases ◽  
Vaccine Development ◽  
Forecast Period ◽  
Phase 3 ◽  
Plasma Therapy ◽  
Vaccine Candidates ◽  
Market Growth ◽  
University Of Oxford ◽  
Prevention Trials

The global COVID-19 vaccines market is projected to reach USD 1,401 million by 2025 from USD 2,273 million in 2022, at a CAGR of -14.9% during the forecast period. The growth of the COVID vaccines market is attributed majorly to the rising number of people infected with COVID-19 and increasing funding for vaccine development. On the other hand, the global COVID-19 drugs market is projected to reach USD 2 million by 2025 from USD 165 million in 2020, at a CAGR of -57.8% during the forecast period. The growth of the COVID drugs market is primarily attributed to use of repurposed drugs for compassionate use, and the emergence of alternative therapies such as convalescent plasma therapy which were earlier used for treating epidemic diseases such as SARS, MERS, and H1N1. Moreover, collaborations between global organizations and governments of various nations to promote the supply of essential drugs and medical supplies are fueling the market growth. Researchers worldwide are working around the clock to find a vaccine against SARS-CoV-2, the virus causing the COVID-19 pandemic. The Herculean effort means that a fast-tracked vaccine could come to market anywhere from the end of 2020 to the middle of 2021. To date, just two coronavirus vaccine has been approved. Sputnik V – formerly known as Gam-COVID-Vac and developed by the Gamaleya Research Institute in Moscow – was approved by the Ministry of Health of the Russian Federation on 11 August. Experts have raised considerable concern about the vaccine’s safety and efficacy given it has not yet entered Phase 3 clinical trials. A second vaccine in Russia, EpiVacCorona, has also been granted regulatory approval, also without entering Phase 3 clinical trials. Operation Warp Speed (OWS) is a collaboration of several US federal government departments including Health and Human Services and its subagencies, Agriculture, Energy and Veterans Affairs and the private sector. OWS has selected three vaccine candidates to fund for Phase 3 trials: Moderna’s mRNA-1273, University of Oxford and AstraZeneca’s AZD1222, and Pfizer and BioNTech's BNT162. Within OWS, the US National Institutes of Health (NIH) has partnered with more than 18 biopharmaceutical companies to accelerate development of drug and vaccine candidates for COVID-19 (ACTIV). The COVID-19 Prevention Trials Network (COVPN) has also been established, which combines clinical trial networks funded by the National Institute of Allergy and Infectious Diseases (NIAID): the HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network (HPTN), Infectious Diseases Clinical Research Consortium (IDCRC), and the AIDS Clinical Trials Group.

scholarly journals Ebolavirus: Comparison of Survivor Immunology and Animal Models in the Search for a Correlate of Protection

2021 ◽  
Vol 11 ◽  
Author(s):  
Stephanie Longet ◽  
Jack Mellors ◽  
Miles W. Carroll ◽  
Tom Tipton
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Immune Responses ◽  
Ebola Virus ◽  
Democratic Republic ◽  
Vaccine Development ◽  
Democratic Republic Of Congo ◽  
Virus Disease ◽  
Correlate Of Protection ◽  
Host Immune Responses

Ebola viruses are enveloped, single-stranded RNA viruses belonging to the Filoviridae family and can cause Ebola virus disease (EVD), a serious haemorrhagic illness with up to 90% mortality. The disease was first detected in Zaire (currently the Democratic Republic of Congo) in 1976. Since its discovery, Ebola virus has caused sporadic outbreaks in Africa and was responsible for the largest 2013–2016 EVD epidemic in West Africa, which resulted in more than 28,600 cases and over 11,300 deaths. This epidemic strengthened international scientific efforts to contain the virus and develop therapeutics and vaccines. Immunology studies in animal models and survivors, as well as clinical trials have been crucial to understand Ebola virus pathogenesis and host immune responses, which has supported vaccine development. This review discusses the major findings that have emerged from animal models, studies in survivors and vaccine clinical trials and explains how these investigations have helped in the search for a correlate of protection.

Sign in / Sign up

Export Citation Format

Share Document