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Microbes and Infection 2018Vaccines are one of the most important methods for preventing infectious disease. Structural modification of lipopolysaccharide (LPS) provides a strategy for the... (Review)
Review
Vaccines are one of the most important methods for preventing infectious disease. Structural modification of lipopolysaccharide (LPS) provides a strategy for the development of live attenuated vaccines, either by altering the immunogenicity or by attenuating virulence of the bacteria. This review summarizes various approaches that utilize LPS mutants as whole-cell vaccines.
Topics: Animals; Bacterial Vaccines; Gram-Negative Bacteria; Humans; Lipid A; Lipopolysaccharides; Mutation; O Antigens; Oligosaccharides; Vaccines, Attenuated
PubMed: 29233768
DOI: 10.1016/j.micinf.2017.11.006 -
Parasitology Oct 2009The high level of protection which can be induced by vaccination of a range of hosts, from rodents to primates, with live radiation-attenuated schistosome larvae offers... (Review)
Review
The high level of protection which can be induced by vaccination of a range of hosts, from rodents to primates, with live radiation-attenuated schistosome larvae offers great promise for development of a human schistosome vaccine. Studies of the irradiated vaccine models benefitted from significant funding during the 1970-90s and much was learned concerning the inducers, targets and mechanisms of immunity. Less progress was made in definition of the protective antigens involved. The application of new techniques for identifying membrane and secreted antigens has recently provided new vaccine candidates and a new impetus for schistosome vaccine development. This article is intended as an overview of some of the main lessons learned from the studies of the irradiated vaccines as a backdrop to renewed interest in schistosome vaccine development.
Topics: Animals; Antibodies, Helminth; Disease Models, Animal; Gamma Rays; Humans; Mice; Rats; Schistosoma; Schistosomiasis; Vaccination; Vaccines, Attenuated
PubMed: 19327194
DOI: 10.1017/S0031182009005848 -
Frontiers in Cellular and Infection... 2022Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute watery diarrhea and vomiting in unweaned piglets. Infections result in high mortality...
Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute watery diarrhea and vomiting in unweaned piglets. Infections result in high mortality and serious economic losses to the swine industry. PEDV attenuated vaccine does not completely protect against all mutant wild-type strains, and PEDV infection can periodically occur. A sensitive, accurate, and simple detection method for PEDV is needed to reduce the occurrence of the disease. In this study, the CRISPR/Cas13a system was combined with recombinase aided amplification to develop a rapid diagnostic method to distinguish PEDV wild-type strains from attenuated vaccine strains. The method is based on isothermal detection at 37°C. The results are used for visual readout. The assay had high sensitivity and specificity, with a detection limit of 10 copies/μL for the gene of interest, and no cross-reactivity with other pathogens. The Cas13a detection worked well with clinical samples. This visual, sensitive, and specific nucleic acid detection method based on CRISPR/Cas13a should be a powerful tool for detecting PEDV.
Topics: Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Coronavirus Infections; Diarrhea; Nucleic Acids; Porcine epidemic diarrhea virus; Recombinases; Sensitivity and Specificity; Swine; Swine Diseases; Vaccines, Attenuated
PubMed: 36176580
DOI: 10.3389/fcimb.2022.976137 -
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 -
Pharmaceutical Research Oct 2014Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and... (Review)
Review
Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and humoral immune responses is a major challenge. Recent studies have demonstrated that antigen delivery via nanoparticle formulations can significantly improve immunogenicity of vaccines due to either intrinsic immunostimulatory properties of the materials or by co-entrapment of molecular adjuvants such as Toll-like receptor agonists. These studies have collectively shown that nanoparticles designed to mimic biophysical and biochemical cues of pathogens offer new exciting opportunities to enhance activation of innate immunity and elicit potent cellular and humoral immune responses with minimal cytotoxicity. In this review, we present key research advances that were made within the last 5 years in the field of nanoparticle vaccine delivery systems. In particular, we focus on the impact of biomaterials composition, size, and surface charge of nanoparticles on modulation of particle biodistribution, delivery of antigens and immunostimulatory molecules, trafficking and targeting of antigen presenting cells, and overall immune responses in systemic and mucosal tissues. This review describes recent progresses in the design of nanoparticle vaccine delivery carriers, including liposomes, lipid-based particles, micelles and nanostructures composed of natural or synthetic polymers, and lipid-polymer hybrid nanoparticles.
Topics: Adaptive Immunity; Animals; Biocompatible Materials; Drug Carriers; Humans; Immunity, Innate; Liposomes; Micelles; Nanoparticles; Particle Size; Surface Properties; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 24848341
DOI: 10.1007/s11095-014-1419-y -
Frontiers in Cellular and Infection... 2018is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay"... (Review)
Review
is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay" vaccine, subunit vaccines comprising protein(s) or lipoproteins(s) in an adjuvant formulation, and the Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals-especially mice-but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including . Since live attenuated-but not killed or subunit-vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies or , or against non-respiratory challenge with virulent subsp. (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. , the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. , and subsp. , and heterologous vaccines developed using viral or bacterial vectors to express immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development-safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the higher standard of having efficacy ≥LVS in the demanding mouse model of tularemia. These latter include LVS with deletions in , or ; LVS Δ that also overexpresses Type VI Secretion System (T6SS) proteins; FSC200 with a deletion in ; the single deletional mutant of SCHU S4, and a heterologous prime-boost vaccine comprising LVS Δ and expressing T6SS proteins.
Topics: Animals; Bacterial Capsules; Bacterial Proteins; Bacterial Vaccines; Bioterrorism; Disease Models, Animal; Francisella tularensis; Heat-Shock Proteins; Humans; Lipoproteins; Listeria monocytogenes; Mice; Oxidative Stress; Sequence Deletion; Superoxide Dismutase; Tularemia; Type VI Secretion Systems; Vaccines, Attenuated; Vaccines, Subunit; Virulence
PubMed: 29868510
DOI: 10.3389/fcimb.2018.00154 -
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 -
Virologica Sinica Oct 2022Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and...
Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar mice that lack type I IFN receptor. Following intravenous injection, the H2 failed to cause obvious clinical symptoms in Ifnar mice, and no significant upregulation in serum alanine aminotransferase (ALT) levels was observed. Notably, the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area, but no focal necrosis was observed in liver tissues. Viral RNAs sustained in the liver, and the infectious virus could be recovered from the liver tissue until 42 days post-infection. More importantly, H2 infection induced obvious viremia and persistent viral shedding in feces. In addition, robust HAV-specific humoral immune responses were induced in Ifnar mice. Overall, our study revealed the safety profile of H2 in Ifnar mice, which not only helps understand the attenuation mechanism of H2, but also expands the application of the Ifnar mouse model for HAV studies.
Topics: Animals; Humans; Mice; Alanine Transaminase; Hepatitis A virus; Interferon Type I; Receptor, Interferon alpha-beta; Vaccines, Attenuated; Virulence
PubMed: 35863604
DOI: 10.1016/j.virs.2022.07.009 -
Human Vaccines & Immunotherapeutics 2014Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal... (Review)
Review
Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq(®) and Rotarix(®) are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants' acute gastroenteritis.
Topics: Gastroenteritis; Humans; Immunity, Mucosal; Incidence; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 25424826
DOI: 10.4161/hv.29605 -
Human Vaccines Jan 2010Malaria remains one of the most significant infectious diseases affecting human populations in developing countries. The quest for an efficacious malaria vaccine has... (Review)
Review
Malaria remains one of the most significant infectious diseases affecting human populations in developing countries. The quest for an efficacious malaria vaccine has been ongoing for nearly a century with limited success. The identification of malaria parasite antigens focused efforts on the development of subunit vaccines but has so far yielded only one partially efficacious vaccine candidate, RTS/S. The lack of high vaccine efficacy observed to date with subunit vaccine candidates raises doubts that the development of a single antigen or even a multi-antigen malaria subunit vaccine is possible. Fortunately, it has been demonstrated in animal studies and experimental clinical studies that immunizations with live-attenuated sporozoite stages of the malaria parasite confer long lasting, sterile protection against infection, providing a benchmark for vaccine development. These early successful vaccinations with live-attenuated malaria parasites did not however, promote a developmental path forward for such a vaccine approach. The discovery of genetically engineered parasite strains that are fully attenuated during the early asymptomatic liver infection and confer complete sterile protection in animal malaria models support the development of a live attenuated sporozoite vaccine for Plasmodium falciparum and its accelerated safety and efficacy testing in malaria challenge models and in malaria endemic areas.
Topics: Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Sporozoites; Vaccines, Attenuated
PubMed: 19838068
DOI: 10.4161/hv.6.1.9654