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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 -
The American Journal of Tropical... Jan 2021sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 10 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 10 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7-13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.
Topics: Adolescent; Adult; Aged; Animals; Antibodies, Protozoan; Antimalarials; Child; Child, Preschool; Chloroquine; Double-Blind Method; Equatorial Guinea; Female; Humans; Immunization; Immunogenicity, Vaccine; Infant; Malaria Vaccines; Malaria, Falciparum; Male; Middle Aged; Parasitemia; Plasmodium falciparum; Vaccines, Attenuated; Young Adult
PubMed: 33205741
DOI: 10.4269/ajtmh.20-0435 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2023Development of a vaccine that can simultaneously induce effective mucosal immunity and systemic immunity is an ideal goal to prevent mucosal pathogenic infections. The... (Review)
Review
Development of a vaccine that can simultaneously induce effective mucosal immunity and systemic immunity is an ideal goal to prevent mucosal pathogenic infections. The digestive tract has many sites for inducing mucosal immunity, including the mouth, stomach and small intestine. An ideal oral viral vaccine can not only induce better local and distal mucosal immunity, but also produce better systemic immunity. The oral viral vaccine has also attracted much attention because of its painless vaccination, self-administration and other advantages. Due to the complexity of human digestive tract environment and mucosal immunity, only three oral attenuated live vaccines have been successfully marketed for human use. This review summarizes the characteristics of gastrointestinal mucosal immunity, the current types and research status of oral viral vaccines, and the challenges faced by oral viral vaccines, with the hope to facilitate the research and development of oral viral vaccines for human use in China.
Topics: Humans; Viral Vaccines; Vaccination; Immunity, Mucosal; Vaccines, Attenuated; Vaccine Development
PubMed: 37805837
DOI: 10.13345/j.cjb.220960 -
Methods in Molecular Biology (Clifton,... 2022Ensuring the maximum standards of quality and welfare in animal production requires developing effective tools to halt and prevent the spread of the high number of... (Review)
Review
Ensuring the maximum standards of quality and welfare in animal production requires developing effective tools to halt and prevent the spread of the high number of infectious diseases affecting animal husbandry. Many of these diseases are caused by pathogens of viral etiology. To date, one of the best strategies is to implement preventive vaccination policies whenever possible. However, many of the currently manufactured animal vaccines still rely in classical vaccine technologies (killed or attenuated vaccines). Under some circumstances, these vaccines may not be optimal in terms of safety and immunogenicity, nor adequate for widespread application in disease-free countries at risk of disease introduction. One step ahead is needed to improve and adapt vaccine manufacturing to the use of new generation vaccine technologies already tested in experimental settings. In the context of viral diseases of veterinary interest, we overview current vaccine technologies that can be approached, with a brief insight in the type of immunity elicited.
Topics: Animals; Vaccination; Vaccines, Attenuated; Viral Vaccines; Virus Diseases
PubMed: 35118613
DOI: 10.1007/978-1-0716-2168-4_1 -
Applied Microbiology and Biotechnology Jun 2021As the reality of pandemic threats challenges humanity, exemplified during the ongoing SARS-CoV-2 infections, the development of vaccines targeting these etiological... (Review)
Review
As the reality of pandemic threats challenges humanity, exemplified during the ongoing SARS-CoV-2 infections, the development of vaccines targeting these etiological agents of disease has become increasingly critical. Of paramount concern are novel and reemerging pathogens that could trigger such events, including the plague bacterium Yersinia pestis. Y. pestis is responsible for more human deaths than any other known pathogen and exists globally in endemic regions of the world, including the four corners region and Northern California in the USA. Recent cases have been scattered throughout the world, including China and the USA, with serious outbreaks in Madagascar during 2008, 2013-2014, and, most recently, 2017-2018. This review will focus on recent advances in plague vaccine development, a seemingly necessary endeavor, as there is no Food and Drug Administration-licensed vaccine available for human distribution in western nations, and that antibiotic-resistant strains are recovered clinically or intentionally developed. Progress and recent development involving subunit, live-attenuated, and nucleic acid-based plague vaccine candidates will be discussed in this review. KEY POINTS: • Plague vaccine development remains elusive yet critical. • DNA, animal, and live-attenuated vaccine candidates gain traction.
Topics: Animals; Antibodies, Bacterial; COVID-19; China; Humans; Plague; Plague Vaccine; SARS-CoV-2; Vaccines, Attenuated; Yersinia pestis
PubMed: 34142207
DOI: 10.1007/s00253-021-11389-6 -
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 -
Fish & Shellfish Immunology Dec 2022Nocardia seriolae, a Gram-positive facultative intercellular pathogen, has been identified as the causative agent of fish nocardiosis, causing substantial mortality and...
Nocardia seriolae, a Gram-positive facultative intercellular pathogen, has been identified as the causative agent of fish nocardiosis, causing substantial mortality and morbidity of a wide range of fish species. Looking into that fact, the effective vaccine against this pathogen is urgently needed to control the significant losses in aquaculture practices. In order to induct attenuated strains for developing the potential live vaccines, the mutagenic N. seriolae strain S-250 and U-20 were obtained from wild-type strain ZJ0503 through continuous passaging and ultraviolet (UV) irradiation, respectively. Additionally, the biological characteristic, virulence, stability, mediating immune response and supplying protective efficacy to hybrid snakehead of the S-250 and U-20 strains were determined in the present study. The results showed that U-20 strain displayed dramatic changes in morphological characteristic and significant decreased in the virulence to hybrid snakehead, while that of S-250 strain had no obvious different in comparison to ZJ0503 strain. When hybrid snakehead were intraperitoneally injected with ZJ0503, S-250 and U-20 strains at their respective sub-clinical dosage, the non-specific immunity parameters (serum LYZ, POD, ACP, AKP and SOD activities), specific antibody (IgM) titers production and immune-related genes (CC1, CC2, IL-1β, IL-8, TNFα, IFNγ, MHCIα, MHCIIα, CD4, CD8α, TCRα and TCRβ) expression were up-regulated, indicating that they were able to trigger humoral and cell-mediated immune responses. Furthermore, the protective efficacy in hybrid snakehead after vaccination with ZJ0503, S-250 and U-20 strains, in terms of relative percentage survival (RPS), were 28.85%, 56.89% and 89.65% respectively. Taken together, two attenuated N. seriolae strains S-250 and U-20 were obtained successfully and they could elicit strong immune response and supply protective efficacy to hybrid snakehead against N. seriolae, which suggested that these two attenuated strains were the potential candidates for live vaccine development to control fish nocardiosis in aquaculture.
Topics: Animals; Fish Diseases; Nocardia; Nocardia Infections; Fishes; Vaccines, Attenuated
PubMed: 36162777
DOI: 10.1016/j.fsi.2022.09.053 -
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 -
PloS One 2019Currently, influenza vaccine manufacturers need to produce 1-5 x 107 PFU of each vaccine strain to fill one dose of the current live-attenuated-influenza-vaccine (LAIV)....
Currently, influenza vaccine manufacturers need to produce 1-5 x 107 PFU of each vaccine strain to fill one dose of the current live-attenuated-influenza-vaccine (LAIV). To make a single dose of inactivated vaccine (15 ug of each hemagglutinin), the equivalent of 1010 PFU of each vaccine strains need to be grown. This high dose requirement is a major drawback for manufacturing as well as rapidly sourcing sufficient doses during a pandemic. Using our computer-aided vaccine platform Synthetic Attenuated Virus Engineering (SAVE), we created a vaccine candidate against pandemic H1N1 A/CA/07/2009 (CodaVax-H1N1) with robust efficacy in mice and ferrets, and is protective at a much lower dose than the current LAIV. CodaVax-H1N1 is currently in Phase I/II clinical trials. The hemagglutinin (HA) and neuraminidase (NA) gene segments of A/California/07/2009 (H1N1) (CA07) were "de-optimized" and a LAIV was generated ex silico using DNA synthesis. In DBA/2 mice, vaccination at a very low dose (100 or approximately 1 PFU) with CodaVax-H1N1 prevented disease after lethal challenge with wild-type H1N1. In BALB/c mice, as little as 103 PFU was protective against lethal challenge with mouse-adapted H1N1. In ferrets, CodaVax-H1N1 was more potent compared to currently licensed LAIV and still effective at a low dose of 103 PFU at preventing replication of challenge virus.
Topics: Animals; Computer-Aided Design; Disease Models, Animal; Ferrets; Hemagglutinin Glycoproteins, Influenza Virus; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Neuraminidase; Vaccination; Vaccines, Attenuated; Viral Proteins
PubMed: 31609986
DOI: 10.1371/journal.pone.0223784 -
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