scholarly journals Current Status of Zika Virus Vaccines: Successes and Challenges

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 266 ◽  
Author(s):  
Aryamav Pattnaik ◽  
Bikash R. Sahoo ◽  
Asit K. Pattnaik
Keyword(s):  
Zika Virus ◽  
Viral Infections ◽  
Current Status ◽  
Effective Vaccine ◽  
Congenital Diseases ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Nucleic Acid Vaccines ◽  
Funding Agencies ◽  
Inactivated Vaccines

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs.

scholarly journals Current Progress in the Development of Zika Virus Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1004
Author(s):  
Kehui Zhou ◽  
Chaoqun Li ◽  
Wen Shi ◽  
Xiaodan Hu ◽  
Kutty Selva Nandakumar ◽  
...  
Keyword(s):  
Zika Virus ◽  
Large Scale ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Effective Vaccine ◽  
Zikv Infection ◽  
Teratogenic Effects ◽  
Subunit Vaccines ◽  
Live Attenuated Vaccines ◽  
Inactivated Vaccines

Zika virus (ZIKV) is an arbovirus first discovered in the Americas. ZIKV infection is insidious based on its mild clinical symptoms observed after infection. In Brazil, after 2015, ZIKV infection broke out on a large scale, and many infected pregnant women gave birth to babies with microcephaly. The teratogenic effects of the virus on the fetus and its effects on nerves and the immune system have attracted great attention. Currently, no specific prophylactics or therapeutics are clinically available to treat ZIKV infection. Development of a safe and effective vaccine is essential to prevent the rise of any potential pandemic. In this review, we summarize the latest research on Zika vaccine development based on different strategies, including DNA vaccines, subunit vaccines, live-attenuated vaccines, virus-vector-based vaccines, inactivated vaccines, virus-like particles (VLPs), mRNA-based vaccines, and others. We anticipate that this review will facilitate further progress toward the development of effective and safe vaccines against ZIKV infection.

scholarly journals Development of a potent Zika virus vaccine using self-amplifying messenger RNA

2020 ◽  
Vol 6 (32) ◽  
pp. eaba5068 ◽  
Author(s):  
Kate Luisi ◽  
Kaitlyn M. Morabito ◽  
Katherine E. Burgomaster ◽  
Mayuri Sharma ◽  
Wing-Pui Kong ◽  
...  
Keyword(s):  
Zika Virus ◽  
Messenger Rna ◽  
Protective Immunity ◽  
Nonhuman Primates ◽  
Neutralizing Antibody ◽  
Effective Vaccine ◽  
Proof Of Concept ◽  
Zikv Infection ◽  
Vaccine Candidates ◽  
Rapid Responses

Zika virus (ZIKV) is the cause of a pandemic associated with microcephaly in newborns and Guillain-Barre syndrome in adults. Currently, there are no available treatments or vaccines for ZIKV, and the development of a safe and effective vaccine is a high priority for many global health organizations. We describe the development of ZIKV vaccine candidates using the self-amplifying messenger RNA (SAM) platform technology delivered by cationic nanoemulsion (CNE) that allows bedside mixing and is particularly useful for rapid responses to pandemic outbreaks. Two immunizations of either of the two lead SAM (CNE) vaccine candidates elicited potent neutralizing antibody responses to ZIKV in mice and nonhuman primates. Both SAM (CNE) vaccines protected these animals from ZIKV challenge, with one candidate providing complete protection against ZIKV infection in nonhuman primates. The data provide a preclinical proof of concept that a SAM (CNE) vaccine candidate can rapidly elicit protective immunity against ZIKV.

scholarly journals A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1371
Author(s):  
Priscila M. S. Castanha ◽  
Ernesto T. A. Marques
Keyword(s):  
Clinical Trials ◽  
Clinical Efficacy ◽  
Vaccine Development ◽  
Global Scale ◽  
Causal Link ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Nucleic Acid Vaccines ◽  
Future Challenges ◽  
Potential Vaccine

The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a safe and effective Zika vaccine. Multiple vaccine platforms, including purified inactivated virus, nucleic acid vaccines, live-attenuated vaccines, and viral-vectored vaccines, have advanced to human clinical trials. In this review, we discuss the recent advances in the field of Zika vaccine development and the challenges for future clinical efficacy trials. We provide a brief overview on Zika vaccine platforms in the pipeline before summarizing the vaccine candidates in clinical trials, with a focus on recent, promising results from vaccine candidates that completed phase I trials. Despite low levels of transmission during recent years, ZIKV has become endemic in the Americas and the potential of large Zika outbreaks remains real. It is important for vaccine developers to continue developing their Zika vaccines, so that a potential vaccine is ready for deployment and clinical efficacy trials when the next ZIKV outbreak occurs.

scholarly journals Prediction of CD8 and CD4 T cell epitopes in the polyprotein of Zika Virus; an immunoinformatics approach

2018 ◽  
Author(s):  
Tahreem Zaheer ◽  
Muhammad Talha Shahid Khan ◽  
Hamza Arshad Dar ◽  
Shifa Tariq Ashraf ◽  
Rehan Zafar Paracha ◽  
...  
Keyword(s):  
T Cell ◽  
Zika Virus ◽  
Viral Infections ◽  
Consensus Sequence ◽  
Experimental Studies ◽  
Cd4 T Cell ◽  
Binding Affinities ◽  
T Cell Epitopes ◽  
Vaccine Candidates ◽  
Global Threat

Background: Zika virus (ZIKV) is an arbovirus that belongs to family Flaviviridae. The virus has emerged as a global threat and no FDA approved vaccine is available, so an efficient vaccine needs to be designed in order to prevent the infection. Computationally designed vaccines can be used for broad-spectrum therapeutics as they can evoke response against viral infections. In the current study, we have predicted antigenic promiscuous T cell epitopes from Zika virus polyprotein using a range of immune-informatics tools and servers. Methods: A total of 238 polyprotein sequences derived from 238 complete genomes were retrieved using NIAID Virus Pathogen Resource and multiple aligned. Using a consensus sequence, the promiscuous CD8-T cell epitopes were predicted from Propred I and CTLPred and their binding affinities were determined by NetMHC4.0. CD4-T cell epitopes were predicted using ProPred and the binding affinities were determined by MHCPred. Antigenicity score and Immunogenicity score was determined from Vaxijen 2.0 and IEDB immunogenicity tool. Homology was found by pBLAST. Results: Among 78 predicted HLA-I binding epitopes, 19 highly antigenic, immunogenic and high-affinity epitopes are prioritized among which 15 are novel vaccine candidates. However, 66 strong HLA-II interacting T cell epitopes are pooled out from 70 predicted epitopes. Among the shortlisted CD4-T cell epitopes 56 epitopes are novel. Conclusion: Epitope-based vaccines are robust and promising candidates against bacterial and viral infections. The predicted epitopes can serve as potential vaccine candidates. Our study shows promising epitopes that can be used to generate stimulate active immune responses in the majority of the human population around the world, However, our results need validation through experimental studies for confirmation.

scholarly journals Prediction of CD8 and CD4 T cell epitopes in the polyprotein of Zika Virus; an immunoinformatics approach

2018 ◽  
Author(s):  
Tahreem Zaheer ◽  
Muhammad Talha Shahid Khan ◽  
Hamza Arshad Dar ◽  
Shifa Tariq Ashraf ◽  
Rehan Zafar Paracha ◽  
...  
Keyword(s):  
T Cell ◽  
Zika Virus ◽  
Viral Infections ◽  
Consensus Sequence ◽  
Experimental Studies ◽  
Cd4 T Cell ◽  
Binding Affinities ◽  
T Cell Epitopes ◽  
Vaccine Candidates ◽  
Global Threat

Background: Zika virus (ZIKV) is an arbovirus that belongs to family Flaviviridae. The virus has emerged as a global threat and no FDA approved vaccine is available, so an efficient vaccine needs to be designed in order to prevent the infection. Computationally designed vaccines can be used for broad-spectrum therapeutics as they can evoke response against viral infections. In the current study, we have predicted antigenic promiscuous T cell epitopes from Zika virus polyprotein using a range of immune-informatics tools and servers. Methods: A total of 238 polyprotein sequences derived from 238 complete genomes were retrieved using NIAID Virus Pathogen Resource and multiple aligned. Using a consensus sequence, the promiscuous CD8-T cell epitopes were predicted from Propred I and CTLPred and their binding affinities were determined by NetMHC4.0. CD4-T cell epitopes were predicted using ProPred and the binding affinities were determined by MHCPred. Antigenicity score and Immunogenicity score was determined from Vaxijen 2.0 and IEDB immunogenicity tool. Homology was found by pBLAST. Results: Among 78 predicted HLA-I binding epitopes, 19 highly antigenic, immunogenic and high-affinity epitopes are prioritized among which 15 are novel vaccine candidates. However, 66 strong HLA-II interacting T cell epitopes are pooled out from 70 predicted epitopes. Among the shortlisted CD4-T cell epitopes 56 epitopes are novel. Conclusion: Epitope-based vaccines are robust and promising candidates against bacterial and viral infections. The predicted epitopes can serve as potential vaccine candidates. Our study shows promising epitopes that can be used to generate stimulate active immune responses in the majority of the human population around the world, However, our results need validation through experimental studies for confirmation.

scholarly journals Broadly Neutralizing Antibodies for HIV-1 Prevention

2021 ◽  
Vol 12 ◽  
Author(s):  
Stephen R. Walsh ◽  
Michael S. Seaman
Keyword(s):  
Neutralizing Antibodies ◽  
Passive Immunization ◽  
Lessons Learned ◽  
Current Status ◽  
Effective Vaccine ◽  
Broadly Neutralizing Antibodies ◽  
Efficacy Trials ◽  
Cd4 Binding Site ◽  
Preclinical Animal Models ◽  
Hiv 1

Given the absence of an effective vaccine for protection against HIV-1 infection, passive immunization strategies that utilize potent broadly neutralizing antibodies (bnAbs) to block acquisition of HIV-1 are being rigorously pursued in the clinical setting. bnAbs have demonstrated robust protection in preclinical animal models, and several leading bnAb candidates have shown favorable safety and pharmacokinetic profiles when tested individually or in combinations in early phase human clinical trials. Furthermore, passive administration of bnAbs in HIV-1 infected individuals has resulted in prolonged suppression of viral rebound following interruption of combination antiretroviral therapy, and robust antiviral activity when administered to viremic individuals. Recent results from the first efficacy trials testing repeated intravenous administrations of the anti-CD4 binding site bnAb VRC01 have demonstrated positive proof of concept that bnAb passive immunization can confer protection against HIV-1 infection in humans, but have also highlighted the considerable barriers that remain for such strategies to effectively contribute to control of the epidemic. In this review, we discuss the current status of clinical studies evaluating bnAbs for HIV-1 prevention, highlight lessons learned from the recent Antibody Mediated Prevention (AMP) efficacy trials, and provide an overview of strategies being employed to improve the breadth, potency, and durability of antiviral protection.

scholarly journals A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Izabela K Ragan ◽  
Lindsay M Hartson ◽  
Taru S Dutt ◽  
Andres Obregon-Henao ◽  
Rachel M Maison ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Rapid Development ◽  
Neutralizing Antibody ◽  
Emerging Diseases ◽  
Effective Vaccine ◽  
Preliminary Evaluation ◽  
Sequencing Data ◽  
Post Challenge ◽  
Vaccine Candidates ◽  
The Impact

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

scholarly journals Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 774
Author(s):  
Chengfeng Gao ◽  
Chunxia Wen ◽  
Zhifeng Li ◽  
Shuhan Lin ◽  
Shu Gao ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Rna Virus ◽  
Emerging Viruses ◽  
Enterovirus A71 ◽  
Ic50 Values ◽  
High Doses ◽  
Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

scholarly journals Mass Spectrometry versus Conventional Techniques of Protein Detection: Zika Virus NS3 Protease Activity towards Cellular Proteins

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3732
Author(s):  
Agnieszka Dabrowska ◽  
Aleksandra Milewska ◽  
Joanna Ner-Kluza ◽  
Piotr Suder ◽  
Krzysztof Pyrc
Keyword(s):  
Mass Spectrometry ◽  
Zika Virus ◽  
Viral Infections ◽  
Protein Detection ◽  
Extensive Discussion ◽  
Protein Targets ◽  
Highly Sensitive ◽  
Infected Cells ◽  
Ns3 Protease ◽  
To Receive

Mass spectrometry (MS) used in proteomic approaches is able to detect hundreds of proteins in a single assay. Although undeniable high analytical power of MS, data acquired sometimes lead to confusing results, especially during a search of very selective, unique interactions in complex biological matrices. Here, we would like to show an example of such confusing data, providing an extensive discussion on the observed phenomenon. Our investigations focus on the interaction between the Zika virus NS3 protease, which is essential for virus replication. This enzyme is known for helping to remodel the microenvironment of the infected cells. Several reports show that this protease can process cellular substrates and thereby modify cellular pathways that are important for the virus. Herein, we explored some of the targets of NS3, clearly shown by proteomic techniques, as processed during infection. Unfortunately, we could not confirm the biological relevance of protein targets for viral infections detected by MS. Thus, although mass spectrometry is highly sensitive and useful in many instances, also being able to show directions where cell/virus interaction occurs, we believe that deep recognition of their biological role is essential to receive complete insight into the investigated process.

scholarly journals Towards Improved Use of Vaccination in the Control of Infectious Bronchitis and Newcastle Disease in Poultry: Understanding the Immunological Mechanisms

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 20
Author(s):  
Anthony C. Ike ◽  
Chukwuebuka M. Ononugbo ◽  
Okechukwu J. Obi ◽  
Chisom J. Onu ◽  
Chinasa V. Olovo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Newcastle Disease ◽  
Viral Infections ◽  
Advanced Technology ◽  
Global Food Security ◽  
Infectious Bronchitis ◽  
Immunological Mechanisms ◽  
Inactivated Vaccines ◽  
Successful Control ◽  
Cellular Immune

Infectious bronchitis (IB) and Newcastle disease (ND) are two important diseases of poultry and have remained a threat to the development of the poultry industry in many parts of the world. The immunology of avian has been well studied and numerous vaccines have been developed against the two viruses. Most of these vaccines are either inactivated vaccines or live attenuated vaccines. Inactivated vaccines induce weak cellular immune responses and require priming with live or other types of vaccines. Advanced technology has been used to produce several types of vaccines that can initiate prime immune responses. However, as a result of rapid genetic variations, the control of these two viral infections through vaccination has remained a challenge. Using various strategies such as combination of live attenuated and inactivated vaccines, development of IB/ND vaccines, use of DNA vaccines and transgenic plant vaccines, the problem is being surmounted. It is hoped that with increasing understanding of the immunological mechanisms in birds that are used in fighting these viruses, a more successful control of the diseases will be achieved. This will go a long way in contributing to global food security and the economic development of many developing countries, given the role of poultry in the attainment of these goals.

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