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Frontiers in Cellular and Infection... 2023is the common pathogen affecting various species of marine organisms. It has been demonstrated that is a necessary virulence factor to adhere and infect their hosts...
is the common pathogen affecting various species of marine organisms. It has been demonstrated that is a necessary virulence factor to adhere and infect their hosts for pathogenic bacteria. Frequent disease outbreaks in aquaculture have highlighted the necessity of developing effective vaccines. In the present study, in order to investigate the function of in , the deletion mutant Δ was constructed and its biological properties were evaluated, additionally, the differences in gene expression levels between wild-type and Δ were analyzed by transcriptomics. Finally, Δ was used as a live attenuated vaccine to immunize grouper via the intraperitoneal route to evaluate its protective effect. Results show that gene of was identified as being 783 bp in length, encoding 260 amino acids, and showing significant similarity to homologs of other species. The -deletion mutant Δ of was successfully constructed, and its biological phenotype analysis showed no significant differences in growth capacity and extracellular enzyme activity compared to the wild-type. However, a substantial reduction of motility ability was detected in Δ. Transcriptomic analysis revealed that the absence of gene is responsible for a significantly decreased expression of flagellar genes, including , , , and . The -deletion mainly affects the related pathways involved in cell motility, membrane transport, signal transduction, carbohydrate metabolism, and amino acid metabolism in . The efficacy of Δ as a candidate of live attenuated vaccine were evaluated by intraperitoneal injection in grouper. The Δ provided the RPS (Relative protection rate) of 67.2% against in groupers. The Δ efficiently stimulated antibody production with specific IgM still detected at 42 d post-vaccination, and significantly elevated the activity of antioxidant enzymes like Catalase (CAT), Superoxide dismutase (SOD), and lactate dehydrogenase (LDH) in the serum. The higher expression levels of immune-related genes were observed in the immune tissues of inoculated grouper compared to the control. In conclusion, Δ effectively improved the immunity of inoculated fish. The results suggest that Δ is an effective live attenuated vaccine against vibriosis in in grouper.
Topics: Animals; Vibrio alginolyticus; Vaccines, Attenuated; Fishes; Vibrio Infections; Virulence Factors; Fish Diseases; Bacterial Vaccines
PubMed: 37180437
DOI: 10.3389/fcimb.2023.1162299 -
International Journal of Molecular... Jun 2022Influenza is still a frequent seasonal infection of the upper respiratory tract, which may have deadly consequences, especially for the elderly. This is in spite of the... (Review)
Review
Influenza is still a frequent seasonal infection of the upper respiratory tract, which may have deadly consequences, especially for the elderly. This is in spite of the availability of vaccines suggested for persons above 65 years of age. Two types of conventional influenza vaccines are currently licensed for use-live attenuated and inactivated vaccines. Depending on local regulatory requirements, live attenuated vaccines are produced by the reverse genetics technique or by classical reassortment in embryonated chicken eggs. Sometimes, the efficiency of classical reassortment is complicated by certain properties of the wild-type parent virus. Cases of low efficacy of vaccines have been noted, which, among other reasons, may be associated with suboptimal properties of the wild-type parent virus that are not considered when recommendations for influenza vaccine composition are made. Unfortunately, knowledge surrounding the roles of properties of the circulating influenza virus and its impact on the efficacy of the reassortment process, vaccination efficiency, the infectivity of the vaccine candidates, etc., is now scattered in different publications. This review summarizes the main features of the influenza virus that may dramatically affect different aspects of the preparation of egg-derived live attenuated vaccine candidates and their effectiveness. The author expresses her personal view, which may not coincide with the opinion of other experts in the field of influenza vaccines.
Topics: Aged; Female; Humans; Influenza Vaccines; Influenza, Human; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 35743258
DOI: 10.3390/ijms23126815 -
Journal of Virology Feb 2015Although live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still...
UNLABELLED
Although live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston-Zagreb (EZ), allowing recovery of recombinant (r)MV(EZ). Three recombinant viruses were generated that contained the open reading frame encoding enhanced green fluorescent protein (EGFP) within an additional transcriptional unit (ATU) at various positions within the genome. rMV(EZ)EGFP(1), rMV(EZ)EGFP(3), and rMV(EZ)EGFP(6) contained the ATU upstream of the N gene, following the P gene, and following the H gene, respectively. The viruses were compared in vitro by growth curves, which indicated that rMV(EZ)EGFP(1) was overattenuated. Intratracheal infection of cynomolgus macaques with these recombinant viruses revealed differences in immunogenicity. rMV(EZ)EGFP(1) and rMV(EZ)EGFP(6) did not induce satisfactory serum antibody responses, whereas both in vitro and in vivo rMV(EZ)EGFP(3) was functionally equivalent to the commercial MV(EZ)-containing vaccine. Intramuscular vaccination of macaques with rMV(EZ)EGFP(3) resulted in the identification of EGFP(+) cells in the muscle at days 3, 5, and 7 postvaccination. Phenotypic characterization of these cells demonstrated that muscle cells were not infected and that dendritic cells and macrophages were the predominant target cells of live-attenuated MV.
IMPORTANCE
Even though MV strain Edmonston-Zagreb has long been used as a live-attenuated vaccine (LAV) to protect against measles, nothing is known about the primary cells in which the virus replicates in vivo. This is vital information given the push to move toward needle-free routes of vaccination, since vaccine virus replication is essential for vaccination efficacy. We have generated a number of recombinant MV strains expressing enhanced green fluorescent protein. The virus that best mimicked the nonrecombinant vaccine virus was formulated according to protocols for production of commercial vaccine virus batches, and was subsequently used to assess viral tropism in nonhuman primates. The virus primarily replicated in professional antigen-presenting cells, which may explain why this LAV is so immunogenic and efficacious.
Topics: Animals; Dendritic Cells; Genes, Reporter; Green Fluorescent Proteins; Macaca fascicularis; Macrophages; Male; Measles Vaccine; Measles virus; Muscles; Staining and Labeling; Vaccines, Attenuated
PubMed: 25473055
DOI: 10.1128/JVI.02924-14 -
The Cochrane Database of Systematic... Jun 2018Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective.
OBJECTIVES
To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017.
SELECTION CRITERIA
RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane.
MAIN RESULTS
We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.
Topics: Aged; Disease Progression; Humans; Influenza Vaccines; Influenza, Human; Lung Diseases, Obstructive; Randomized Controlled Trials as Topic; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 29943802
DOI: 10.1002/14651858.CD002733.pub3 -
Human Vaccines & Immunotherapeutics Dec 2024Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly... (Review)
Review
Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.
Topics: Humans; Vaccines, Attenuated; HIV Infections; Herpes Zoster Vaccine; Vaccines, Synthetic; Herpes Zoster; Vaccines, Inactivated; Immunogenicity, Vaccine; Vaccine Efficacy; Herpesvirus 3, Human; Adult; Child; Vaccination; Chickenpox Vaccine
PubMed: 38650460
DOI: 10.1080/21645515.2024.2341456 -
Vaccine Jul 2014Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to... (Review)
Review
Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.
Topics: Drug Discovery; Genetic Engineering; Humans; Salmonella Vaccines; Technology, Pharmaceutical; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 24370705
DOI: 10.1016/j.vaccine.2013.12.026 -
The Cochrane Database of Systematic... Jul 2007Vaccination is recognized as the only practical measure for preventing Japanese encephalitis. Production shortage, costs, and issues of licensure impair vaccination... (Review)
Review
BACKGROUND
Vaccination is recognized as the only practical measure for preventing Japanese encephalitis. Production shortage, costs, and issues of licensure impair vaccination programmes in many affected countries. Concerns over vaccine effectiveness and safety also have a negative impact on acceptance and uptake.
OBJECTIVES
To evaluate vaccines for preventing Japanese encephalitis in terms of effectiveness, adverse events, and immunogenicity.
SEARCH STRATEGY
In March 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 1), MEDLINE, EMBASE, LILACS, BIOSIS, and reference lists. We also attempted to contact corresponding authors and vaccine companies.
SELECTION CRITERIA
Randomized controlled trials (RCTs), including cluster-RCTs, comparing Japanese encephalitis vaccines with placebo (inert agent or unrelated vaccine), no intervention, or alternative Japanese encephalitis vaccine.
DATA COLLECTION AND ANALYSIS
Authors independently extracted data and assessed methodological quality. Dichotomous data were compared with relative risks and a 95% confidence interval (CI), and converted into percentage vaccine efficacy.
MAIN RESULTS
Eight RCTs involving 358,750 participants were included. These trials investigated two available and three pre-licensure vaccines. Two RCTs assessing efficacy of the commercially available inactivated Nakayama vaccine were identified. A two-dose schedule of the licensed vaccine provided significant protection of 95% (95% CI 10% to 100%) for one year only, while two doses of an unpurified precursor vaccine protected children by 81% (95% CI 45% to 94%) in year one and by 59% (95% CI 2% to 83%) in year two. Serious adverse events were not observed. Mild and moderate episodes of injection site soreness, fever, headache, and nausea were reported in less than 6% of children receiving inactivated vaccine compared to 0.6% of unvaccinated controls. One cluster-RCT compared the live-attenuated SA14-14-2 vaccine (widely used in China) with no intervention measuring adverse events. Fever was reported in 2.7% of vaccinees compared to 3.1% of controls, while 0.1% of both groups suffered diarrhoea or seizures. Four small pre-licensure RCTs assessing a genetically engineered vaccine and two cell culture-derived inactivated vaccines revealed high immunogenicity and relative safety.
AUTHORS' CONCLUSIONS
Only one of the three currently used vaccines has been assessed for efficacy in a RCT. Other RCTs have assessed their safety, however, and they appear to cause only occasional mild or moderate adverse events. Further trials of effectiveness and safety are needed for the currently used vaccines, especially concerning dose levels and schedules. Trials investigating several new vaccines are planned or in progress.
Topics: Encephalitis, Japanese; Humans; Japanese Encephalitis Vaccines; Randomized Controlled Trials as Topic; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 17636750
DOI: 10.1002/14651858.CD004263.pub2 -
Clinical Microbiology Reviews Jan 2008Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood... (Review)
Review
Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.
Topics: Administration, Oral; Animals; Cattle; Child, Preschool; Clinical Trials as Topic; Europe; Humans; Infant; Intussusception; Latin America; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Treatment Outcome; United States; Vaccination; Vaccines, Attenuated
PubMed: 18202442
DOI: 10.1128/CMR.00029-07 -
Vaccine Mar 2020Despite a critical need for a respiratory syncytial virus (RSV) vaccine and decades of development efforts, a vaccine to protect infants, elderly, and other at-risk...
Despite a critical need for a respiratory syncytial virus (RSV) vaccine and decades of development efforts, a vaccine to protect infants, elderly, and other at-risk populations from RSV infection remains elusive. We have previously generated a new, live-attenuated vaccine candidate against RSV using rational, computer-aided gene design and chemical synthesis through a process termed viral gene "deoptimization." In this study, we assessed the attenuation, immunogenicity, and efficacy of this synthetic, live-attenuated RSV vaccine candidate, RSV-MinL4.0, in African Green Monkeys. RSV-MinL4.0 was produced under good-manufacturing-practice (GMP) in Vero cells. Vaccination with RSV-MinL4.0 resulted in minimal virus shedding after vaccination, generation of robust humoral and cellular immune responses (despite the presence of baseline RSV neutralizing antibodies in one animal) that were comparable to a wildtype infection, and protection from virus shedding post-challenge with wildtype RSV. These findings demonstrate the promise of RSV-MinL4.0 as a live-attenuated vaccine which will undergo clinical trials to test its ability to safely and effectively protect pediatric and elderly populations from infection with RSV.
Topics: Animals; Antibodies, Viral; Chlorocebus aethiops; Codon; Computer-Aided Design; Immunity, Cellular; Immunity, Humoral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccines, Attenuated; Vero Cells
PubMed: 32107060
DOI: 10.1016/j.vaccine.2020.02.056 -
Viruses Oct 2016Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration... (Review)
Review
Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.
Topics: Animals; Antiviral Agents; Biological Products; Drug Discovery; Humans; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Vaccines, Attenuated
PubMed: 27801824
DOI: 10.3390/v8110279