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Biomedicine & Pharmacotherapy =... Dec 2021Dengue virus (DENV) is a global health threat causing about half of the worldwide population to be at risk of infection, especially the people living in tropical and...
Dengue virus (DENV) is a global health threat causing about half of the worldwide population to be at risk of infection, especially the people living in tropical and subtropical area. Although the dengue disease caused by dengue virus (DENV) is asymptomatic and self-limiting in most people with first infection, increased severe dengue symptoms may be observed in people with heterotypic secondary DENV infection. Since there is a lack of specific antiviral medication, the development of dengue vaccines is critical in the prevention and control this disease. Several targets and strategies in the development of dengue vaccine have been demonstrated. Currently, Dengvaxia, a live-attenuated chimeric yellow-fever/tetravalent dengue vaccine (CYD-TDV) developed by Sanofi Pasteur, has been licensed and approved for clinical use in some countries. However, this vaccine has demonstrated low efficacy in children and dengue-naïve individuals and also increases the risk of severe dengue in young vaccinated recipients. Accordingly, many novel strategies for the dengue vaccine are under investigation and development. Here, we conducted a systemic literature review according to PRISMA guidelines to give a concise overview of various aspects of the vaccine development process against DENVs, mainly targeting five potential strategies including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral-vector vaccine, and DNA vaccine. This study offers the comprehensive view of updated information and current progression of immunogen selection as well as strategies of vaccine development against DENVs.
Topics: Animals; Dengue; Dengue Vaccines; Dengue Virus; Humans; Treatment Outcome; Vaccine Development; Vaccine Efficacy; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Inactivated; Vaccines, Synthetic; Viral Envelope Proteins; Viral Nonstructural Proteins
PubMed: 34634560
DOI: 10.1016/j.biopha.2021.112304 -
Microbiology Spectrum Dec 2022To develop safe and highly effective live vaccines, rational vaccine design is necessary. Here, we sought a simple approach to rationally develop a safe attenuated...
To develop safe and highly effective live vaccines, rational vaccine design is necessary. Here, we sought a simple approach to rationally develop a safe attenuated vaccine against the genome-reduced pathogen Erysipelothrix rhusiopathiae. We examined the mRNA expression of all conserved amino acid biosynthetic genes remaining in the genome after the reductive evolution of . Reverse transcription-quantitative PCR (qRT-PCR) analysis revealed that half of the 14 genes examined were upregulated during the infection of murine J774A.1 macrophages. Gene deletion was possible only for three proline biosynthesis genes, , , and , the last of which was upregulated 29-fold during infection. Five mutants bearing an in-frame deletion of one (Δ, Δ, or Δ mutant), two (Δ mutant), or three (Δ mutant) genes exhibited attenuated growth during J774A.1 infection, and the attenuation and vaccine efficacy of these mutants were confirmed in mice and pigs. Thus, for the rational design of live vaccines against genome-reduced bacteria, the selective targeting of genes that escaped chromosomal deletions during evolution may be a simple approach for identifying genes which are specifically upregulated during infection. Identification of bacterial genes that are specifically upregulated during infection can lead to the rational construction of live vaccines. For this purpose, genome-based approaches, including DNA microarray analysis and IVET ( expression technology), have been used so far; however, these methods can become laborious and time-consuming. In this study, we used a simple approach and showed that in genome-reduced bacteria, the genes which evolutionarily remained conserved for metabolic adaptations during infection may be the best targets for the deletion and construction of live vaccines.
Topics: Swine; Animals; Mice; Vaccines, Attenuated; Erysipelothrix; Macrophages; Bacterial Vaccines
PubMed: 36453908
DOI: 10.1128/spectrum.03776-22 -
Vaccine Aug 2021Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox...
Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox has emerged as the most threatening bio-terrorism agent; as the first- and second-generation smallpox vaccines have been controversial and have caused severe adverse reactions, new demands for safe smallpox vaccines have been raised and some attenuated smallpox vaccines have been developed. We have developed a cell culture-based highly attenuated third-generation smallpox vaccine candidate KVAC103 strain by 103 serial passages of the Lancy-Vaxina strain derived from the Lister in Vero cells. Several clones were selected, taking into consideration their shape, size, and growth rate in mammalian cells. The clones were then inoculated intracerebrally in suckling mice to test for neurovirulence by observing survival. Protective immune responses in adult mice were examined by measuring the levels of neutralization antibodies and IFN-γ expression. Among several clones, clone 7 was considered the best alternative candidate because there was no mortality in suckling mice against a lethal challenge. In addition, enhanced neutralizing antibodies and T-cell mediated IFN-γ production were observed in clone 7-immunized mice. Clone 7 was named "KVAC103" and was used for the skin toxicity test and full-genome analysis. KVAC103-inoculated rabbits showed reduced skin lesions compared to those inoculated with the Lister strain, Lancy-Vaxina. A whole genome analysis of KVAC103 revealed two major deleted regions that might contribute to the reduced virulence of KVAC103 compared to the Lister strain. Phylogenetic inference supported the close relationship with the Lister strain. Collectively, our data demonstrate that KVAC103 holds promise for use as a third-generation smallpox vaccine strain due to its enhanced safety and efficacy.
Topics: Animals; Antibodies, Viral; Chlorocebus aethiops; Mice; Mice, Inbred BALB C; Phylogeny; Rabbits; Smallpox; Smallpox Vaccine; Vaccines, Attenuated; Vaccinia virus; Variola virus; Vero Cells
PubMed: 34334254
DOI: 10.1016/j.vaccine.2021.06.060 -
Microbial Pathogenesis Sep 2021African swine fever (ASF) is an acute, hemorrhagic and severe infectious disease caused by African swine fever virus (ASFV) in domestic pigs and various wild boars, with... (Review)
Review
African swine fever (ASF) is an acute, hemorrhagic and severe infectious disease caused by African swine fever virus (ASFV) in domestic pigs and various wild boars, with a mortality rate up to 100%. ASF was first discovered in 1921 in Kenya. ASFV has a large genome and complex immune escape mechanism creating difficulties in the production of vaccines. Recently, remarkable advances have been made in vaccine development all over the world especially in live-attenuated vaccine. This article aims to review the research progress of ASF attenuated live vaccines in order to provide a reference for the development of vaccines for this disease.
Topics: African Swine Fever; African Swine Fever Virus; Animals; Humans; Sus scrofa; Swine; Vaccines, Attenuated; Viral Vaccines
PubMed: 34089790
DOI: 10.1016/j.micpath.2021.105024 -
Journal of Translational Medicine Feb 2024Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer affecting the adult population. Median overall survival for GBM patients is poor...
Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer affecting the adult population. Median overall survival for GBM patients is poor (15 months), primarily due to high rates of tumour recurrence and the paucity of treatment options. Oncolytic virotherapy is a promising treatment alternative for GBM patients, where engineered viruses selectively infect and eradicate cancer cells by inducing cell lysis and eliciting robust anti-tumour immune response. In this study, we evaluated the oncolytic potency of live-attenuated vaccine strains of Zika virus (ZIKV-LAV) against human GBM cells in vitro. Our findings revealed that Axl and integrin αβ function as cellular receptors mediating ZIKV-LAV infection in GBM cells. ZIKV-LAV strains productively infected and lysed human GBM cells but not primary endothelia and terminally differentiated neurons. Upon infection, ZIKV-LAV mediated GBM cell death via apoptosis and pyroptosis. This is the first in-depth molecular dissection of how oncolytic ZIKV infects and induces death in tumour cells.
Topics: Humans; Zika Virus; Oncolytic Viruses; Zika Virus Infection; Glioblastoma; Vaccines, Attenuated; Neoplasm Recurrence, Local; Oncolytic Virotherapy
PubMed: 38308299
DOI: 10.1186/s12967-024-04930-4 -
Frontiers in Immunology 2023Tuberculosis (TB) remains a serious public health threat around the world. An effective vaccine is urgently required for cost-effective, long-term control of TB.... (Review)
Review
Tuberculosis (TB) remains a serious public health threat around the world. An effective vaccine is urgently required for cost-effective, long-term control of TB. However, the only licensed vaccine Bacillus Calmette-Guerin (BCG) is limited to prevent TB for its highly variable efficacy. Substantial progress has been made in research and development (R&D) of TB vaccines in the past decades, and a dozen vaccine candidates, including live attenuated mycobacterial vaccines, killed mycobacterial vaccines, adjuvanted subunit vaccines, viral vector vaccines, and messenger RNA (mRNA) vaccines were developed in clinical trials to date. Nevertheless, many challenges to the successful authorization for the use and deployment of an effective tuberculosis vaccine remain. Therefore, it is still necessary and urgent to continue exploring new vaccine construction approaches. Virus-like particles (VLPs) present excellent prospects in the field of vaccine development because of their helpful immunological features such as being safe templates without containing viral nucleic acid, repetitive surface geometry, conformational epitopes similar to natural viruses, and enhancing both innate and adaptive immune responses. The marketization process of VLP vaccines has never stopped despite VLP vaccines face several shortcomings such as their complex and slow development process and high production cost, and several VLP-based vaccines, including vaccines against Human papillomavirus (HPV), Hepatitis B Virus (HBV) and malaria, are successfully licensed for use at the market. In this review, we provide an update on the current progress regarding the development of TB vaccines in clinical trials and seek to give an overview of VLP-based TB vaccine candidates.
Topics: Humans; Mycobacterium bovis; Tuberculosis; Tuberculosis Vaccines; Vaccines, Attenuated; Vaccines, Virus-Like Particle; Viral Vaccines; Clinical Trials as Topic
PubMed: 38022657
DOI: 10.3389/fimmu.2023.1238649 -
Journal of Virology Oct 2022Together with inactivated influenza vaccines (IIV), live attenuated influenza vaccines (LAIV) are an important tool to prevent influenza A virus (IAV) illnesses in...
Together with inactivated influenza vaccines (IIV), live attenuated influenza vaccines (LAIV) are an important tool to prevent influenza A virus (IAV) illnesses in patients. LAIVs present the advantages to have a needle-free administration and to trigger a mucosal immune response. LAIV is approved for healthy 2- to 49-year old individuals. However, due to its replicative nature and higher rate of adverse events at-risk populations are excluded from the benefits of this vaccine. Using targeted mutagenesis, we modified the nonstructural protein 1 of the currently licensed LAIV in order to impair its ability to bind the host cellular protein CPSF30 and thus its ability to inhibit host mRNA poly-adenylation. We characterized our optimized LAIV (optiLAIV) in three different mouse models mimicking healthy and high-risk patients. Using a neonatal mouse model, we show faster clearance of our optimized vaccine compared to the licensed LAIV. Despite lower replication, optiLAIV equally protected mice against homosubtypic and hetesubtypic influenza strain challenges. We confirmed the safer profile of optiLAIV in Stat1 mice (highly susceptible to viral infections) by showing no signs of morbidity compared to a 50% mortality rate observed following LAIV inoculation. Using a human nasal 3D tissue model, we showed an increased induction of ER stress-related genes following immunization with optiLAIV. Induction of ER stress was previously shown to improve antigen-specific immune responses and is proposed as the mechanism of action of the licensed adjuvant AS03. This study characterizes a safer LAIV candidate in two mouse models mimicking infants and severely immunocompromised patients and proposes a simple attenuation strategy that could broaden LAIV application and reduce influenza burden in high-risk populations. Live attenuated influenza vaccine (LAIV) is a needle-free, mucosal vaccine approved for healthy 2- to 49-year old individuals. Its replicative nature and higher rate of adverse events excludes at-risk populations. We propose a strategy to improve LAIV safety and explore the possibility to expand its applications in children under 2-year old and immunocompromised patients. Using a neonatal mouse model, we show faster clearance of our optimized vaccine (optiLAIV) compared to the licensed LAIV. Despite lower replication, optiLAIV equally protected mice against influenza virus challenges. We confirmed the safer profile of optiLAIV in Stat1 mice (highly susceptible to viral infections) by showing no signs of morbidity compared to a 50% mortality rate from LAIV. OptiLAIV could expand the applications of the current LAIV and help mitigate the burden of IAV in susceptible populations.
Topics: Child; Infant; Humans; Mice; Animals; Child, Preschool; Adolescent; Young Adult; Adult; Middle Aged; Influenza Vaccines; Influenza, Human; Antibodies, Viral; Vaccines, Attenuated; Vaccines, Inactivated; Influenza A virus; RNA, Messenger
PubMed: 36190240
DOI: 10.1128/jvi.00871-22 -
Science Progress 2022Despite the development and deployment of effective COVID-19 vaccines, many regions remain poorly covered. Seeking alternative tools for achieving immunity against... (Review)
Review
Despite the development and deployment of effective COVID-19 vaccines, many regions remain poorly covered. Seeking alternative tools for achieving immunity against COVID-19 remains to be of high importance. "Trained immunity" is the nonspecific immune response usually established through administering live attenuated vaccines and is a potential preventive tool against unrelated infections. Evidence regarding a possible protective role for certain live attenuated vaccines against COVID-19 has emerged mainly for those administered as part of childhood vaccination protocols. This review summarizes the relevant literature about the potential impact of Bacille Calmette-Guérin (BCG) and measles, mumps and rubella (MMR) vaccines on COVID-19. Existing available data suggest a potential role for BCG and MMR in reducing COVID-19 casualties and burden. However, more investigation and comparative studies are required for a better understanding of their impact on COVID-19 outcomes.
Topics: BCG Vaccine; COVID-19; COVID-19 Vaccines; Humans; Measles-Mumps-Rubella Vaccine; Mumps; Rubella; Vaccination; Vaccines, Attenuated
PubMed: 35848578
DOI: 10.1177/00368504221105172 -
Clinical Microbiology and Infection :... Dec 2019Epidemiological and immunological studies are increasingly reporting non-specific effects (NSEs) of vaccines; i.e. vaccines may affect the risk and severity of... (Review)
Review
BACKGROUND
Epidemiological and immunological studies are increasingly reporting non-specific effects (NSEs) of vaccines; i.e. vaccines may affect the risk and severity of non-targeted infections. We reviewed how epidemiological studies developed the concept of beneficial NSEs of live vaccines.
SOURCES
This is a personal narrative of how we came to pursue the concept of NSEs in studies of measles vaccine (MV) from the late 1970s. We also searched Pubmed for epidemiological studies of nonspecific/non-specific effects (NSEs) of the most common human vaccines.
CONTENT
When smallpox vaccine was introduced around 1800, bacillus Calmette-Guérin (BCG) against tuberculosis in the 1920s and oral polio vaccine (OPV) in the 1960s, there were suggestions that these live attenuated vaccines reduced mortality more than expected. However, scientific follow-up was limited and the concept of beneficial NSEs did not become mainstream. We observed beneficial NSEs after MV was introduced in low-income countries in the 1970s. Subsequent observational studies and randomized trials confirmed beneficial NSEs of smallpox vaccine, BCG and OPV. Recently, beneficial NSEs have been claimed for the non-live diphtheria-tetanus-pertussis and rabies vaccines. However, no non-live vaccine has yet been documented to produce beneficial NSEs.
IMPLICATIONS
Observational and experimental research has shown beneficial NSEs of four live attenuated vaccines: smallpox vaccine, BCG, OPV and MV. With immunological evidence now supporting the epidemiological observations, it is urgent to take both the specific and NSEs into account in the planning of vaccination programmes.
Topics: Clinical Studies as Topic; Cross Protection; Female; Humans; Male; Mortality; Sex Factors; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 31449870
DOI: 10.1016/j.cmi.2019.08.011 -
Journal of Applied Microbiology Dec 2021Salmonella spp. are important human pathogens globally causing millions of cases of typhoid fever and non-typhoidal salmonellosis annually. There are only a few vaccines... (Review)
Review
Salmonella spp. are important human pathogens globally causing millions of cases of typhoid fever and non-typhoidal salmonellosis annually. There are only a few vaccines licensed for use in humans which all target Salmonella enterica serovar Typhi. Vaccine development is hampered by antigenic diversity between the thousands of serovars capable of causing infection in humans. However, a number of attenuated candidate vaccine strains are currently being developed. As facultative intracellular pathogens with multiple systems for transporting effector proteins to host cells, attenuated Salmonella strains can also serve as ideal tools for the delivery of foreign antigens to create multivalent live carrier vaccines for simultaneous immunization against several unrelated pathogens. Further, the ease with which Salmonella can be genetically modified and the extensive knowledge of the virulence mechanisms of this pathogen means that this bacterium has often served as a model organism to test new approaches. In this review we focus on (1) recent advances in live attenuated Salmonella vaccine development, (2) improvements in expression of foreign antigens in carrier vaccines and (3) adaptation of attenuated strains as sources of purified antigens and vesicles that can be used for subunit and conjugate vaccines or together with attenuated vaccine strains in heterologous prime-boosting immunization strategies. These advances have led to the development of new vaccines against Salmonella which have or will soon be tested in clinical trials.
Topics: Humans; Salmonella; Salmonella Infections; Salmonella Vaccines; Salmonella typhi; Typhoid Fever; Vaccines, Attenuated
PubMed: 33665941
DOI: 10.1111/jam.15055