Vaccines
In 2020 we celebrate 75 years of the anniversary of our founding with a year of activities dedicated to demonstrating the impact of microbiologists’ past, present and future – bringing together and empowering communities that help shape the future of microbiology. We are launching new collections of digital content throughout the anniversary year. The third digital hub is ‘Vaccines: the global challenge for microbiology’, which will explore how vaccines work, how they are produced, herd immunity and disease eradication.
This Vaccine collection brings together the work of our journals on current and future vaccines, how they protect not just humans but animals as well, and how they are created.
Collection Contents
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Generation of a potential koi herpesvirus live vaccine by simultaneous deletion of the viral thymidine kinase and dUTPase genes
Koi herpesvirus (KHV, Cyprinidherpesvirus 3) causes a fatal disease of koi and common carp. To obtain safe and efficacious live vaccines, we generated deletion mutants of KHV lacking the nonessential genes encoding two enzymes of nucleotide metabolism, thymidine kinase (TK, ORF55) and deoxyuridine-triphosphatase (DUT, ORF123). Since single-deletion mutants based on a KHV isolate from Israel (KHV-I) only exhibited partial attenuation (Fuchs W, Fichtner D, Bergmann SM, Mettenleiter TC. Arch Virol 2011;156 : 1059–1063), a corresponding double mutant was generated and tested in vivo, and shown to be almost avirulent but still protective. To overcome the low in vitro virus titres of KHV-I (≤105 p.f.u. ml−1), single and double TK and DUT deletions were also introduced into a cell culture-adapted KHV strain from Taiwan (KHV-T). The deletions did not affect in vitro virus replication, and all KHV-T mutants exhibited wild-type-like plaque sizes and titres exceeding 107 p.f.u. ml−1, as a prerequisite for economic vaccine production. Compared to wild-type and revertant viruses, the single-deletion mutants of KHV-T were significantly attenuated in vivo, and immersion of juvenile carp in water containing high doses of the double mutant caused almost no fatalities. Nevertheless, the deletion mutants induced similar levels of KHV-specific serum antibodies to the parental wild-type virus, and conferred solid protection against disease after challenge with wild-type KHV. For the convenient differentiation of DNA samples prepared from gill swabs of carp infected with wild-type and TK-deleted KHV we developed a triplex real-time PCR. Thus, KHV-TΔDUT/TK might be suitable as a genetic DIVA vaccine in the field.
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Genetic diversity of pneumococcal surface protein A (PspA) in paediatric isolates of non-conjugate vaccine serotypes in Japan
Purpose. Among the pneumococcal proteins, pneumococcal surface protein A (PspA) is considered the most promising candidate for a serotype-independent vaccine. This study aimed to investigate the serotype, genetic diversity of PspA, lineage (genotype) and drug resistance traits of pneumococcal isolates from paediatric patients.
Methodology. A total of 678 non-invasive pneumococcal isolates obtained from June to November 2016 were analysed. All isolates were characterized for PspA families, serotypes and macrolide resistance genes. Seventy-one representative isolates of non-vaccine serotypes (NVTs) were genetically analysed for the clade-defining region (CDR) of PspA, as well as multi-locus sequence typing (MLST).
Results. The detection rate of NVTs was 87.9 % (n=596), including dominant NVTs 15A (14.5 %, n=98), 35B (11.8 %, n=80), 15C (9.3 %, n=63) and 23A (9.0 %, n=61). Most isolates (96.6 %) possessed macrolide resistance genes erm(B) and/or mef(A/E). PspA families 1, 2 and 3 were detected in 42.3, 56.6 and 0.6 % of isolates, respectively. Nucleotide sequences of CDR showed high identity (90–100 %) within the same PspA clade, although the CDR identity among different PspA families ranged from 53 to 69 %. All isolates of NVTs 23A, 10A, 34, 24, 22F/22A, 33F, 23B and 38 were from PspA family 1, while NVTs 35B, 15C, 15B and 11A/11D isolates were from family 2. In contrast, genetically distinct PspAs were found in NVTs 6C and 15A. PspA family 3/clade 6 was detected in only NVT serotype 37 isolates assigned to ST447 and ST7970, showing the mucoid phenotype.
Conclusion. The present study revealed the predominance of PspA families 1 and 2 in NVTs, and the presence of family 3 in serotype 37.
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Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56
The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase ‘antigen’-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications.
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