Viral Vectors for COVID-19 Vaccine Development

Vaccine development against SARS-CoV-2 has been fierce due to the devastating COVID-19 pandemic and has included all potential approaches for providing the global community with safe and efficient vaccine candidates in the shortest possible timeframe. Viral vectors have played a central role especially using adenovirus-based vectors. Additionally, other viral vectors based on vaccinia viruses, measles viruses, rhabdoviruses, influenza viruses and lentiviruses have been subjected to vaccine development. Self-amplifying RNA virus vectors have been utilized for lipid nanoparticle-based delivery of RNA as COVID-19 vaccines. Several adenovirus-based vaccine candidates have elicited strong immune responses in immunized animals and protection against challenges in mice and primates has been achieved. Moreover, adenovirus-based vaccine candidates have been subjected to phase I to III clinical trials. Recently, the simian adenovirus-based ChAdOx1 vector expressing the SARS-CoV-2 S spike protein was approved for use in humans in the UK.

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

10.20944/preprints202107.0261.v1 ◽

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.

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Viral vector-based vaccines against SARS-CoV-2

Exploration of Immunology ◽

10.37349/ei.2021.00020 ◽

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.

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SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽

10.1038/s41541-021-00292-w ◽

2021 ◽

Vol 6 (1) ◽

Cited By ~ 3

Author(s):

Nikolaos C. Kyriakidis ◽

Andrés López-Cortés ◽

Eduardo Vásconez González ◽

Alejandra Barreto Grimaldos ◽

Esteban Ortiz Prado

Keyword(s):

Neutralizing Antibodies ◽

Large Scale ◽

Vaccine Development ◽

Rna Virus ◽

Protein S ◽

Effective Vaccine ◽

Phase 3 ◽

Vaccine Candidates ◽

Advantages And Disadvantages ◽

The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

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Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Vaccines ◽

10.3390/vaccines9050480 ◽

2021 ◽

Vol 9 (5) ◽

pp. 480

Author(s):

Honglei Wang ◽

Yangyang Xu ◽

Wenhai Feng

Keyword(s):

Immune Responses ◽

Reverse Genetics ◽

Vaccine Development ◽

Immune Escape ◽

Rna Virus ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Live Vaccines ◽

Host Immune Responses ◽

Inactivated Vaccines

Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available countermeasures against PRRSV infection. However, challenges still exist as the vaccines are not able to induce broad protection. The reason lies in several facts, mainly the variability of PRRSV and the complexity of the interaction between PRRSV and host immune responses, and overcoming these obstacles will require more exploration. Many novel strategies have been proposed to construct more effective vaccines against this evolving and smart virus. In this review, we will describe the mechanisms of how PRRSV induces weak and delayed immune responses, the current vaccines of PRRSV, and the strategies to develop modified live vaccines using reverse genetics systems.

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Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽

10.3390/v12010125 ◽

2020 ◽

Vol 12 (1) ◽

pp. 125 ◽

Cited By ~ 7

Author(s):

Entao Li ◽

Feihu Yan ◽

Pei Huang ◽

Hang Chi ◽

Shengnan Xu ◽

...

Keyword(s):

Immune Responses ◽

Antibody Response ◽

Rabies Virus ◽

Vaccine Development ◽

Vaccine Candidate ◽

Viral Vector ◽

Vaccine Vector ◽

Vaccine Candidates ◽

Cellular Immune Responses ◽

Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

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Novel Concepts for HIV Vaccine Vector Design

mSphere ◽

10.1128/msphere.00415-17 ◽

2017 ◽

Vol 2 (6) ◽

Cited By ~ 8

Author(s):

Quazim A. Alayo ◽

Nicholas M. Provine ◽

Pablo Penaloza-MacMaster

Keyword(s):

Immune Responses ◽

Viral Vectors ◽

Vaccine Development ◽

Viral Vector ◽

Intracellular Pathogens ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Recent Advances ◽

Robust Adaptive ◽

Selection Of

ABSTRACT The unprecedented challenges of developing effective vaccines against intracellular pathogens such as HIV, malaria, and tuberculosis have resulted in more rational approaches to vaccine development. Apart from the recent advances in the design and selection of improved epitopes and adjuvants, there are also ongoing efforts to optimize delivery platforms. The unprecedented challenges of developing effective vaccines against intracellular pathogens such as HIV, malaria, and tuberculosis have resulted in more rational approaches to vaccine development. Apart from the recent advances in the design and selection of improved epitopes and adjuvants, there are also ongoing efforts to optimize delivery platforms. Viral vectors are the best-characterized delivery tools because of their intrinsic adjuvant capability, unique cellular tropism, and ability to trigger robust adaptive immune responses. However, a known limitation of viral vectors is preexisting immunity, and ongoing efforts are aimed at developing novel vector platforms with lower seroprevalence. It is also becoming increasingly clear that different vectors, even those derived from phylogenetically similar viruses, can elicit substantially distinct immune responses, in terms of quantity, quality, and location, which can ultimately affect immune protection. This review provides a summary of the status of viral vector development for HIV vaccines, with a particular focus on novel viral vectors and the types of adaptive immune responses that they induce.

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SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies

10.1101/2021.01.19.21249840 ◽

2021 ◽

Cited By ~ 4

Author(s):

Dami A. Collier ◽

Anna De Marco ◽

Isabella A.T.M. Ferreira ◽

Bo Meng ◽

Rawlings Datir ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Immune Responses ◽

Antibody Responses ◽

Spike Protein ◽

Binding Motif ◽

Wild Type ◽

Emerging Viruses ◽

Transmission Potential ◽

Amino Acid Mutations ◽

The Uk

AbstractSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.

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

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.635337 ◽

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.

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The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir

10.1101/2020.10.15.325050 ◽

2020 ◽

Author(s):

Yan Zhao ◽

Jing Sun ◽

Yunfei Li ◽

Zhengxuan Li ◽

Yu Xie ◽

...

Keyword(s):

Immune Responses ◽

Rna Polymerase ◽

Vaccine Development ◽

Rna Virus ◽

Innate Immune ◽

Innate Immune Responses ◽

Negative Strand ◽

Sense Strand ◽

Viral Vaccine ◽

Polymerase Inhibitor

AbstractSARS-CoV-2, a positive single-stranded RNA virus, caused the COVID-19 pandemic. During the viral replication and transcription, the RNA dependent RNA polymerase (RdRp) “jumps” along the genome template, resulting in discontinuous negative-stranded transcripts. In other coronaviruses, the negative strand RNA was found functionally relevant to the activation of host innate immune responses. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand. During negative strand synthesis, apart from canonical sub-genomic ORFs, numerous non-canonical fusion transcripts are formed, driven by 3-15 nt sequence homology scattered along the genome but more prone to be inhibited by SARS-CoV-2 RNA polymerase inhibitor Remdesivir. The drug also represses more of the negative than the positive strand synthesis as supported by a mathematic simulation model and experimental quantifications. Overall, this study opens new sights into SARS-CoV-2 biogenesis and may facilitate the anti-viral vaccine development and drug design.One Sentence SummaryStrand-biased transcription of SARS-CoV-2.

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Perspectives on RNA Vaccine Candidates for COVID-19

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.635245 ◽

2021 ◽

Vol 8 ◽

Author(s):

Pobitra Borah ◽

Pran Kishore Deb ◽

Nizar A. Al-Shar’i ◽

Lina A. Dahabiyeh ◽

Katharigatta N. Venugopala ◽

...

Keyword(s):

Viral Vectors ◽

Vaccine Development ◽

Lessons Learned ◽

Public Health Care ◽

World Health ◽

Genetic Sequencing ◽

Vaccine Candidates ◽

Clinical Investigations ◽

Current Outbreak ◽

Health Organization

With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.

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