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Expert Review of Vaccines Sep 2014The intensive use of pertussis vaccines has dramatically reduced the incidence of whooping cough during the 20th century. However, recent outbreaks in countries with... (Review)
Review
The intensive use of pertussis vaccines has dramatically reduced the incidence of whooping cough during the 20th century. However, recent outbreaks in countries with high vaccination coverage illustrate the shortcomings of current vaccination regimens, and immunity induced by the most recent, acellular vaccines wanes much faster than anticipated. As an alternative, live attenuated vaccine candidates have recently been developed in order to mimic natural infection, which induces long-lasting immunity. One of them has successfully completed a Phase I trial in humans and is now undergoing further product and clinical developments. This article describes the development of such vaccines, discusses their advantages over existing vaccines and their interesting bystander properties as powerful anti-inflammatory agents, which widens their potential use far beyond that for protection against whooping cough.
Topics: Clinical Trials, Phase I as Topic; Disease Outbreaks; Drug Discovery; Humans; Pertussis Vaccine; Vaccines, Attenuated; Whooping Cough
PubMed: 25085735
DOI: 10.1586/14760584.2014.942222 -
Viruses Apr 2022African swine fever (ASF) is causing a pandemic affecting swine in a large geographical area of the Eastern Hemisphere, from Central Europe to East and Southeast Asia,... (Review)
Review
African swine fever (ASF) is causing a pandemic affecting swine in a large geographical area of the Eastern Hemisphere, from Central Europe to East and Southeast Asia, and recently in the Americas, the Dominican Republic and Haiti. The etiological agent, ASF virus (ASFV), infects both domestic and wild swine and produces a variety of clinical presentations depending on the virus strain and the genetics of the pigs infected. No commercial vaccines are currently available, although experimental recombinant live attenuated vaccine candidates have been shown to be efficacious in protecting animals against disease when challenged with homologous virulent strains. This review attempts to systematically provide an overview of all the live attenuated strains that have been shown to be experimental vaccine candidates. Moreover, it aims to analyze the development of these vaccine candidates, obtained by deleting specific genes or group of genes, and their efficacy in preventing virus infection and clinical disease after being challenged with virulent isolates. This report summarizes all the experimental vaccine strains that have shown promise against the contemporary pandemic strain of African swine fever.
Topics: African Swine Fever; African Swine Fever Virus; Animals; Swine; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines; Viruses, Unclassified
PubMed: 35632620
DOI: 10.3390/v14050878 -
Microbiology Spectrum Feb 2022Hepatitis-hydropericardium syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in huge economic losses to the poultry...
Hepatitis-hydropericardium syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in huge economic losses to the poultry industry globally. The gene, as a major virulence determiner, is also an important vaccine target against FAdV-4. In this study, we used a CRISPR/Cas9-based homology-dependent recombinant technique to replace the gene with and generate a novel recombinant virus, designated FAdV4-EGFP-rF2. Although FAdV4-EGFP-rF2 showed low replication ability compared to the wild-type FAdV-4 in LMH cells, FAdV4-EGFP-rF2 could effectively replicate in LMH-F2 cells with the expression of Fiber-2. Moreover, FAdV4-EGFP-rF2 was not only highly attenuated in chickens, but also could provide efficient protection against a lethal challenge of FAdV-4. Moreover, FAdV4-EGFP-rF2 without could induce neutralizing antibodies at the same level as FA4-EGFP with . These results clearly demonstrate that although affects the viral replication and pathogenesis of FAdV-4, it is not necessary for virus replication and induction of neutralizing antibodies; these findings provide novel insights into the roles of and highlight as an insertion site for generating live-attenuated FAdV-4 vaccines against FAdV-4 and other pathogens. Among all serotypes of fowl adenovirus, serotypes FAdV-1, FAdV-4, and FAdV-10 are unique members with two genes ( and ). Recent studies reveal that Fiber-1, not Fiber-2, directly triggers viral infection of FAdV-4, whereas Fiber-2, but not Fiber-1, has been identified as the major virulence determiner and an efficient protective immunogen for subunit vaccines. Here, we replaced with to generate a novel recombinant virus, designated FAdV4-EGFP-rF2. and studies on FAdV4-EGFP-rF2 revealed that was not necessary for either virus replication or efficient protection for FAdV-4; these results not only provide a novel live-attenuated vaccine candidate against HHS, but also give new ideas for generating a FAdV-4 based vaccine vector against other pathogens.
Topics: Adenoviridae Infections; Animals; Antibodies, Neutralizing; Antibodies, Viral; Aviadenovirus; Chickens; Poultry Diseases; Vaccines, Attenuated; Viral Proteins; Viral Vaccines
PubMed: 35107364
DOI: 10.1128/spectrum.01436-21 -
Human Vaccines & Immunotherapeutics 2019The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher... (Review)
Review
The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher standards of hygiene. Overcoming these obstacles will require great investment and also time, therefore more effective vaccines should be developed to meet the needs of those who would benefit the most from them. Increasing our current knowledge of mucosal immunity, response to Rotavirus infection and its modulation by circadian rhythms could point at actionable pathways to improve vaccination efficacy, especially in the case of individuals affected by environmental enteropathy. Also, a better understanding and validation of Rotavirus entry factors as well as the systematic monitoring of dominant strains could assist in tailoring vaccines to individual's needs. Another aspect that could improve vaccine efficiency is targeting to M cells, for which new ligands could potentially be sought. Finally, alternative mucosal adjuvants and vaccine expression, storage and delivery systems could have a positive impact in the outcome of Rotavirus vaccination.
Topics: Clinical Trials as Topic; Developing Countries; Enterocytes; Gastroenteritis; Humans; Immunity, Mucosal; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination; Vaccine Potency; Vaccines, Attenuated
PubMed: 30215578
DOI: 10.1080/21645515.2018.1520583 -
Pediatric Nephrology (Berlin, Germany) Dec 2023The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However,... (Review)
Review
The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised.
Topics: Child; Humans; Immunosuppressive Agents; Vaccines, Attenuated; Prospective Studies; Immune System Diseases; Communicable Diseases
PubMed: 37076756
DOI: 10.1007/s00467-023-05969-z -
Biotechnology & Genetic Engineering... Apr 2018The family Rhabdoviridae (RV) comprises a large, genetically diverse collection of single-stranded, negative sense RNA viruses from the order Mononegavirales. Several RV... (Review)
Review
The family Rhabdoviridae (RV) comprises a large, genetically diverse collection of single-stranded, negative sense RNA viruses from the order Mononegavirales. Several RV members are being developed as live-attenuated vaccine vectors for the prevention or treatment of infectious disease and cancer. These include the prototype recombinant Vesicular Stomatitis Virus (rVSV) and the more recently developed recombinant Maraba Virus, both species within the genus Vesiculoviridae. A relatively strong safety profile in humans, robust immunogenicity and genetic malleability are key features that make the RV family attractive vaccine platforms. Currently, the rVSV vector is in preclinical development for vaccination against numerous high-priority infectious diseases, with clinical evaluation underway for HIV/AIDS and Ebola virus disease. Indeed, the success of the rVSV-ZEBOV vaccine during the 2014-15 Ebola virus outbreak in West Africa highlights the therapeutic potential of rVSV as a vaccine vector for acute, life-threatening viral illnesses. The rVSV and rMaraba platforms are also being tested as 'oncolytic' cancer vaccines in a series of phase 1-2 clinical trials, after being proven effective at eliciting immune-mediated tumour regression in preclinical mouse models. In this review, we discuss the biological and genetic features that make RVs attractive vaccine platforms and the development and ongoing testing of rVSV and rMaraba strains as vaccine vectors for infectious disease and cancer.
Topics: Animals; Clinical Trials as Topic; Communicable Disease Control; Communicable Diseases; Genetic Vectors; Humans; Neoplasms; Oncolytic Viruses; Rhabdoviridae; Vaccines, Attenuated
PubMed: 29781359
DOI: 10.1080/02648725.2018.1474320 -
Brazilian Journal of Microbiology :... 2014Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune... (Review)
Review
Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.
Topics: Animals; Bacterial Infections; Bacterial Vaccines; Drug Carriers; Humans; Neoplasms; Organisms, Genetically Modified; Vaccines, Attenuated
PubMed: 25763014
DOI: 10.1590/s1517-83822014000400001 -
Human Vaccines & Immunotherapeutics Nov 2016Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely... (Review)
Review
Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.
Topics: Animals; Drug Carriers; Genetic Vectors; Humans; Influenza Vaccines; Vaccines, Attenuated; Vaccines, Synthetic; Viruses
PubMed: 27455345
DOI: 10.1080/21645515.2016.1210729 -
Methods in Molecular Biology (Clifton,... 2024Creating a safe and effective vaccine against infection by the fungal pathogen Cryptococcus neoformans is an appealing option that complements the discovery of new small...
Creating a safe and effective vaccine against infection by the fungal pathogen Cryptococcus neoformans is an appealing option that complements the discovery of new small molecule antifungals. Recent animal studies have yielded promising results for a variety of vaccines that include live-attenuated and heat-killed whole-cell vaccines, as well as subunit vaccines formulated around recombinant proteins. Some of the recombinantly engineered cryptococcal mutants in the chitosan biosynthesis pathway are avirulent and very effective at conferring protective immunity. Mice vaccinated with these avirulent chitosan-deficient strains are protected from a lethal pulmonary infection with C. neoformans strain KN99. Heat-killed derivatives of the vaccination strains are likewise effective in a murine model of infection. The efficacy of these whole-cell vaccines, however, is dependent on a number of factors, including the inoculation dose, route of vaccination, frequency of vaccination, and the specific mouse strain used in the study. Here, we present detailed methods for identifying and optimizing various factors influencing vaccine potency and efficacy in various inbred mouse strains using a chitosan-deficient cda1Δcda2Δcda3Δ strain as a whole-cell vaccine candidate. This chapter describes the protocols for immunizing three different laboratory mouse strains with vaccination regimens that use intranasal, orotracheal, and subcutaneous vaccination routes after the animals were sedated using two different types of anesthesia.
Topics: Animals; Chitosan; Mice; Fungal Vaccines; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Vaccination; Female; Vaccines, Attenuated
PubMed: 38758333
DOI: 10.1007/978-1-0716-3722-7_27 -
Polish Journal of Veterinary Sciences Mar 2023Despite over 40 years of research on the human immunodeficiency virus type 1 (HIV-1) vaccine, we still lack a considerable progress. Equine infectious anemia virus... (Review)
Review
Despite over 40 years of research on the human immunodeficiency virus type 1 (HIV-1) vaccine, we still lack a considerable progress. Equine infectious anemia virus (EIAV) is a lentivirus in the Retroviridae family, akin to HIV-1 in genome structure and antigenicity. EIA is an important infectious disease in equids, characterized by anemia, persistent infection, and repeated fevers. The EIAV attenuated vaccine in China is the only lentiviral vaccine used on a large scale. Elucidating the mechanism of waning and induction of protective immunity from this attenuated vaccine strain will provide a critical theoretical basis and reference point for vaccine research, particularly in the development of lentivirus vaccines, with far-reaching scientific value and social significance. In this paper, we summarize the information related to EIAV integration site selection, particularly for the Chinese EIAV attenuated vaccine strains on the equine genome. This may improve our mechanistic understanding of EIAV virulence reduction at the host genome level. The obtained data may help elucidate the biological characteristics of EIAV, particularly the Chinese attenuated EIAV vaccine strain, and provide valuable information regarding retroviral infections, particularly lentiviral infection and associated therapeutic vectors.
Topics: Animals; Humans; Equine Infectious Anemia; Horse Diseases; Horses; Infectious Anemia Virus, Equine; Lentiviruses, Equine; Vaccines, Attenuated; Viral Vaccines
PubMed: 36961267
DOI: 10.24425/pjvs.2023.145019