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 Platforms for Production of Protein-Based Vaccines: From Classical to Next-Generation Strategies

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1072
Author(s):  
Raquel Cid ◽  
Jorge Bolívar
Keyword(s):  
Infectious Diseases ◽  
Mammalian Cells ◽  
Vaccine Development ◽  
Low Cost ◽  
Cost Effective ◽  
Insect Larvae ◽  
Subunit Vaccines ◽  
Effective Strategies ◽  
Alternative Systems ◽  
Inactivated Vaccines

To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide. The earliest vaccines were developed as live-attenuated or inactivated pathogens, and, although they still represent the most extended human vaccine types, they also face some issues, such as the potential to revert to a pathogenic form of live-attenuated formulations or the weaker immune response associated with inactivated vaccines. Advances in genetic engineering have enabled improvements in vaccine design and strategies, such as recombinant subunit vaccines, have emerged, expanding the number of diseases that can be prevented. Moreover, antigen display systems such as VLPs or those designed by nanotechnology have improved the efficacy of subunit vaccines. Platforms for the production of recombinant vaccines have also evolved from the first hosts, Escherichia coli and Saccharomyces cerevisiae, to insect or mammalian cells. Traditional bacterial and yeast systems have been improved by engineering and new systems based on plants or insect larvae have emerged as alternative, low-cost platforms. Vaccine development is still time-consuming and costly, and alternative systems that can offer cost-effective and faster processes are demanding to address infectious diseases that still do not have a treatment and to face possible future pandemics.

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

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
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.

scholarly journals Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1319
Author(s):  
Maria del Pilar Martinez Viedma ◽  
Stephen Panossian ◽  
Kennedy Gifford ◽  
Kimberly García ◽  
Isis Figueroa ◽  
...  
Keyword(s):  
Zika Virus ◽  
Clinical Symptoms ◽  
Sampling Period ◽  
Public Health Issue ◽  
Diagnostic Challenge ◽  
Zikv Infection ◽  
Past Infection ◽  
Neurological Sequelae ◽  
Methods Development ◽  
Specificity And Sensitivity

Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces cross-reactive antibodies against other flaviruses. These attributes complicate the ability to differentially diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirus-specific peptides on 339 samples that were previously collected from 6 countries. Overall, we found that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015–2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions. These findings can contribute to ongoing serological methods development and can be adapted for use in future studies.

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 Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 302 ◽  
Author(s):  
Anthony C. Ike ◽  
Chisom J. Onu ◽  
Chukwuebuka M. Ononugbo ◽  
Eleazar E. Reward ◽  
Sophia O. Muo
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Recombinant Dna ◽  
Vaccine Development ◽  
The Body ◽  
Effective Vaccine ◽  
Subunit Vaccines ◽  
Simplex Virus ◽  
Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

Clinical and Epidemiological Features of Acute Zika Virus Infections in León, Nicaragua

2021 ◽  
Author(s):  
Natalie M. Bowman ◽  
Filemón Bucardo ◽  
Matthew H. Collins ◽  
Yaoska Reyes ◽  
Edwing Centeno Cuadra ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sore Throat ◽  
Zika Virus ◽  
Clinical Symptoms ◽  
Laboratory Data ◽  
Maculopapular Rash ◽  
Laboratory Diagnosis ◽  
Zikv Infection ◽  
Serological Tests ◽  
Laboratory Findings

The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in León, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory data may help clinicians suspect ZIKV infection during future outbreaks.

scholarly journals Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Charlotte A. Chang ◽  
Donald J. Hamel ◽  
Wei-Kung Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Vaccine Development ◽  
T Cell Responses ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses

ABSTRACT Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.

scholarly journals Cross-Protection Against Zika Virus Infection Conferred by a Live Attenuated Japanese Encephalitis SA14-14-2 Vaccine

2020 ◽  
Author(s):  
Ran Wang ◽  
Zida Zhen ◽  
Lance Turtle ◽  
Baohua Hou ◽  
Yueqi Li ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Cellular Immunity ◽  
Zika Virus ◽  
T Cell Response ◽  
Encephalitis Virus ◽  
Cross Protection ◽  
World Health ◽  
Effective Vaccine ◽  
Zikv Infection

AbstractZika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection, but did mediate antibody dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue into developing a novel bivalent vaccine against both ZIKV and JEV.ImportanceJapanese encephalitis is a controllable disease in many countries in Asia, especially in China, where many people have Japanese encephalitis virus (JEV) immunity due to extensive JEV vaccination campaigns or natural exposure. Live-attenuated SA14-14-2 strain is a safe and effective vaccine recommended by the World Health Organization and has been vaccinated more than 600 million doses since 1989. As the prevalence of Zika virus (ZIKV) and rising risk in above regions, the cross-reactive immune response between these two antigenically closely related flaviviruses, JEV and ZIKV, should also be fully recognized, which is presumed to be based on those ambiguous cross-reactive immunity between dengue virus and ZIKV. In this study, we found that JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice, which is mainly due to cellular immunity rather than neutralizing antibody response. However, specific protective components or cooperation between components warrant to be explored in subsequent experiments. In conclusion, this study can provide important evidence for those who live in JEV-endemic areas and are at risk for ZIKV infection.

scholarly journals Safety and immunogenicity evaluation of inactivated whole-virus-SARS-COV-2 as emerging vaccine development in Egypt

2021 ◽  
Author(s):  
Amani A Saleh ◽  
Mohamed A Saad ◽  
Islam Ryan ◽  
Magdy Amin ◽  
Mohamed I Shindy ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Neutralizing Antibody ◽  
Positive Development ◽  
Effective Vaccine ◽  
Inactivated Vaccine ◽  
Virus Challenge ◽  
Transmission Electron ◽  
Dose Concentration

Abstract Background Current worldwide pandemic COVID-19 with high numbers of mortality rates and huge economic problems require an urgent demand for safe and effective vaccine development. Inactivated SARS-CoV2 vaccine with alum. Hydroxide can play an important role in reducing the impacts of the COVID-19 pandemic. In this study, vaccine efficacy was evaluated through the detection of the neutralizing antibodies that protect mice from challenge with SARS-CoV 2 three weeks after the 2nd dose. We conclude that the vaccine described here has safety and desirable properties, and our data support further development and plans for clinical trials. Methods Characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069, and MW250352 at GenBank were isolated from Egyptian patients SARS-CoV-2-positive. Development of inactivated vaccine was carried out in a BSL—3 facilities and the immunogenicity was determined in mice at two doses (55 μg and 100 μg per dose). Results The distinct cytopathic effect (CPE) induced by SARS-COV-2 propagation on Vero cell monolayers and the viral particles were identified as Coronaviridae by transmission electron microscopy and RT-PCR on infected cells cultures. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless of the dose concentration, with excellent safety profiles and no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by the wild virus challenge of the vaccinated mice and viral replication detection in lung tissues. Conclusions Vaccinated mice recorded complete protection from challenge infection via inhibition of SARS-COV-2 replication in the lung tissues of mice following virus challenge, regardless of the level of serum neutralizing antibodies. This finding will support future trials for the evaluation of an applicable SARS-CoV-2 vaccine candidate.

scholarly journals Large scale genomic and evolutionary study reveals SARS-CoV-2 virus isolates from Bangladesh strongly correlate with European origin and not with China

2021 ◽  
Author(s):  
Mohammad Fazle Alam Rabbi ◽  
Md. Imran Khan ◽  
Saam Hasan ◽  
Mauricio Chalita ◽  
Kazi Nadim Hasan ◽  
...  
Keyword(s):  
Sore Throat ◽  
Large Scale ◽  
Reference Genome ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Future Research ◽  
P Value ◽  
Raw Data ◽  
Genomic Variants ◽  
Virus Isolates

AbstractRationaleThe global public health is in serious crisis due to emergence of SARS-CoV-2 virus. Studies are ongoing to reveal the genomic variants of the virus circulating in various parts of the world. However, data generated from low- and middle-income countries are scarce due to resource limitation. This study was focused to perform whole genome sequencing of 151 SARS-CoV-2 isolates from COVID-19 positive Bangladeshi patients. The goal of this study was to identify the genomic variants among the SARS-CoV-2 virus isolates in Bangladesh, to determine the molecular epidemiology and to develop a relationship between host clinical trait with the virus genomic variants.MethodSuspected patients were tested for COVID-19 using one step commercial qPCR kit for SARS-CoV-2 Virus. Viral RNA was extracted from positive patients, converted to cDNA which was amplified using Ion AmpliSeq™ SARS-CoV-2 Research Panel. Massive parallel sequencing was carried out using Ion AmpliSeq™ Library Kit Plus. Assembly of raw data is done by aligning the reads to a pre-defined reference genome (NC_045512.2) while retaining the unique variations of the input raw data by creating a consensus genome. A random forest-based association analysis was carried out to correlate the viral genomic variants with the clinical traits present in the host.ResultAmong the 151 viral isolates, we observed the 413 unique variants. Among these 8 variants occurred in more than 80 % of cases which include 241C to T, 1163A to T, 3037C to T,14408C to T, 23403A to G, 28881G to A, 28882 G to A, and finally the 28883G to C. Phylogenetic analysis revealed a predominance of variants belonging to GR clade, which have a strong geographical presence in Europe, indicating possible introduction of the SARS-CoV-2 virus into Bangladesh through a European channel. However, other possibilities like a route of entry from China cannot be ruled out as viral isolate belonging to L clade with a close relationship to Wuhan reference genome was also detected. We observed a total of 37 genomic variants to be strongly associated with clinical symptoms such as fever, sore throat, overall symptomatic status, etc. (Fisher’s Exact Test p-value<0.05). The most mention-worthy among those were the 3916CtoT (associated with causing sore throat, p-value 0.0005), the 14408C to T (associated with protection from developing cough, p-value= 0.027), and the 28881G to A, 28882G to A, and 28883G to C variant (associated with causing chest pain, p-value 0.025).ConclusionTo our knowledge, this study is the first large scale phylogenomic studies of SARS-CoV-2 virus circulating in Bangladesh. The observed epidemiological and genomic features may inform future research platform for disease management, vaccine development and epidemiological study.

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