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Viruses Jun 2023The peste des petits ruminant (PPR) virus is a transboundary virus found in small domestic ruminants that causes high morbidity and mortality in naive herds. PPR can be...
The peste des petits ruminant (PPR) virus is a transboundary virus found in small domestic ruminants that causes high morbidity and mortality in naive herds. PPR can be effectively controlled and eradicated by vaccinating small domestic ruminants with a live-attenuated peste des petits ruminant virus (PPRV) vaccine, which provides long-lasting immunity. We studied the potency and safety of a live-attenuated vaccine in goats by detecting their cellular and humoral immune responses. Six goats were subcutaneously vaccinated with a live-attenuated PPRV vaccine according to the manufacturer's instructions, and two goats were kept in contact. Following vaccination, the goats were monitored daily, and we recorded their body temperature and clinical score. Heparinized blood and serum were collected for a serological analysis, and swab samples and EDTA blood were collected to detect the PPRV genome. The safety of the used PPRV vaccine was confirmed by the absence of PPR-related clinical signs, a negative pen-side test, a low virus genome load as detected with RT-qPCR on the vaccinated goats, and the lack horizontal transmission between the in-contact goats. The strong humoral and cellular immune responses detected in the vaccinated goats showed that the live-attenuated PPRV vaccine has a strong potency in goats. Therefore, live-attenuated vaccines against PPR can be used to control and eradicate PRR.
Topics: Animals; Goat Diseases; Goats; Immunity, Humoral; Peste-des-Petits-Ruminants; Peste-des-petits-ruminants virus; Vaccines, Attenuated
PubMed: 37376624
DOI: 10.3390/v15061325 -
Clinical Microbiology and Infection :... Aug 2019To evaluate the efficacy, safety and immunogenicity of a human diploid cell SV-1 strain-based live attenuated varicella vaccine in children aged 1 to 12 years. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To evaluate the efficacy, safety and immunogenicity of a human diploid cell SV-1 strain-based live attenuated varicella vaccine in children aged 1 to 12 years.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial in China in which healthy children were randomly assigned in a 1:1 ratio to receive one dose of varicella vaccine or placebo. The efficacy monitoring period was 6 to 7 months for each subject. The primary endpoint was the occurrence of laboratory-confirmed varicella. Efficacy and immunity were assessed in the per-protocol cohort, and safety was assessed in the total vaccinated cohort. The file was registered with ClinicalTrials.gov (NCT02981836).
RESULTS
Between 22 August 2016 and 19 September 2016, a total of 5997 children (2997 in the varicella vaccine group and 3000 in the placebo group) were vaccinated, and 5991 children (2995 in the varicella vaccine group and 2996 in the placebo group) were included in the per-protocol efficacy cohort. The efficacy of the vaccine was 87.1% (95% confidence interval, 69.7-94.5) against varicella (six cases vs. 46 cases) and 89.2% (95% confidence interval, 72.9-95.7) breakthrough varicella (five cases vs. 46 cases). No significant difference in solicited adverse reactions was found between the two groups. Serious advent events occurred among 0.8% (25/2998) children in the vaccine group and 0.7% (22/2999) in the placebo group. In the immunogenicity subgroup, the seroconversion rate was 97.1% (339/349) in the vaccine group. An antibody titre of 1:8 was associated with protection against varicella.
CONCLUSIONS
The varicella vaccine was effective in the prevention of varicella in children.
Topics: Antibodies, Viral; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; China; Double-Blind Method; Female; Healthy Volunteers; Humans; Immunogenicity, Vaccine; Infant; Male; Vaccines, Attenuated
PubMed: 30616012
DOI: 10.1016/j.cmi.2018.12.033 -
Virology Journal May 2023Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of...
BACKGROUND
Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections.
METHODS
The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines.
RESULTS
Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits.
CONCLUSIONS
The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.
Topics: Rabbits; Animals; Swine; Herpesvirus 1, Suid; Vaccines, Attenuated; Vaccines, Subunit; Pseudorabies; Adjuvants, Immunologic; GB virus C
PubMed: 37221518
DOI: 10.1186/s12985-023-02051-w -
Frontiers in Immunology 2022Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination... (Review)
Review
Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination stimulates diverse immune responses by mimicking natural infection. Induction of pathogen-specific antibodies or cell-mediated cytotoxicity provides means of specific protection, but LAV can also elicit unintended off-target effects, termed non-specific effects. Such mechanisms as short-lived genetic interference and non-specific innate immune response or long-lasting trained immunity and heterologous immunity allow LAVs to develop resistance to subsequent microbial infections. Based on their safety and potential for interference, LAVs may be considered as an alternative for immediate mitigation and control of unexpected pandemic outbreaks before pathogen-specific therapeutic and prophylactic measures are deployed.
Topics: Immunity; Immunity, Heterologous; Vaccination; Vaccines, Attenuated
PubMed: 35651619
DOI: 10.3389/fimmu.2022.877845 -
PLoS Neglected Tropical Diseases Apr 2024Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas....
Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV.
Topics: Animals; Vaccines, Attenuated; Mice; Chikungunya virus; Viral Vaccines; Chikungunya Fever; Genome, Viral; Antibodies, Viral; Virus Replication; Female; Humans; Chlorocebus aethiops; Antibodies, Neutralizing; Vero Cells; Mice, Inbred BALB C
PubMed: 38648230
DOI: 10.1371/journal.pntd.0012120 -
Virologica Sinica Oct 2014Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory... (Review)
Review
Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.
Topics: Chickenpox; Chickenpox Vaccine; Drug Discovery; Herpes Zoster; Humans; Neuralgia, Postherpetic; Vaccines, Attenuated
PubMed: 25358998
DOI: 10.1007/s12250-014-3516-9 -
Vaccine Dec 2015Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to... (Review)
Review
Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication.
Topics: Adult; Africa; Clinical Trials as Topic; Cryopreservation; Disease Eradication; Europe; Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Sporozoites; Vaccine Potency; Vaccines, Attenuated
PubMed: 26469720
DOI: 10.1016/j.vaccine.2015.09.096 -
Med (New York, N.Y.) Dec 2021In Kenya, the first trial of the attenuated whole organism PfSPZ Vaccine in infants has shown little efficacy against malaria infection, whereas trials in African adults...
In Kenya, the first trial of the attenuated whole organism PfSPZ Vaccine in infants has shown little efficacy against malaria infection, whereas trials in African adults have repeatedly observed protection. Differences in immune responses offer clues to the possible reasons.
Topics: Adult; Clinical Trials as Topic; Humans; Infant; Malaria; Malaria Vaccines; Vaccine Efficacy; Vaccines, Attenuated
PubMed: 35590146
DOI: 10.1016/j.medj.2021.11.002 -
Current Opinion in Virology Oct 2020The Bunyavirales order is the largest group of RNA viruses, which includes important human and animal pathogens, that cause serious diseases. Licensed vaccines are often... (Review)
Review
The Bunyavirales order is the largest group of RNA viruses, which includes important human and animal pathogens, that cause serious diseases. Licensed vaccines are often not available for many of these pathogens. The establishment of bunyavirus reverse genetics systems has facilitated the generation of recombinant infectious viruses, which have been employed as powerful tools for understanding bunyavirus biology and identifying important virulence factors. Technological advances in this area have enabled the development of novel strategies, including codon-deoptimization, viral genome rearrangement and single-cycle replicable viruses, for the generation of live-attenuated vaccine candidates. In this review, we have summarized the current knowledge of the bunyavirus reverse genetics approaches for the generation of live-attenuated vaccine candidates and their evaluation in animal models.
Topics: Animals; Disease Models, Animal; Genome, Viral; Humans; Mice; Orthobunyavirus; Reverse Genetics; Vaccines, Attenuated; Viral Vaccines; Virulence Factors; Virus Replication
PubMed: 32619950
DOI: 10.1016/j.coviro.2020.05.004 -
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