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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Impact of the introduction of a 13-valent pneumococcal vaccine on pneumococcal serotypes in non-invasive isolates from 2007 to 2016 at a teaching hospital in Japan
Purpose. To prevent severe invasive pneumococcal infection, pneumococcal conjugate vaccines (PCVs) were introduced in Japan in 2010, and in 2013 a pneumococcal 13-valent conjugate vaccine (PCV13) was included in the routine vaccination schedule for infants. In this study, we analysed the antimicrobial susceptibilities and capsular types of pneumococci isolated from non-invasive patient sites from 2007 to 2016 to assess the impact of the introduction of PCV13.
Methodology. A total of 618 pneumococcal isolates collected at a teaching hospital from 2007 to 2016 were used. These isolates were characterized by capsular typing, multilocus sequence typing and antimicrobial susceptibility testing.
Results. Capsular typing indicated that, after the introduction of the PCV, the proportion of PCV13 serotypes decreased (P<0.01), while non-PCV13 serotypes became diverse. In particular, increases in 22 F, 15A and 23A were noted among non-PCV13 serotypes. Regarding antimicrobial susceptibility, the non-susceptibility rate to penicillin of pneumococci that showed higher minimum inhibitory concentrations (MICs) than the susceptibility breakpoint decreased, and pneumococci tended to become susceptible. However, all type 23A pneumococci and 77.8 % of type 15A pneumococci showed the reverse trend, with low susceptibility to penicillin. Furthermore, all 15A and 23A isolates had macrolide resistance genes.
Conclusion. These data suggest that PCVs can prevent infections caused by PCV serotypes. However, since non-PCV13-type pneumococci, in particular 15A and 23A, which have acquired multidrug resistance, have already emerged over time, the development of a novel vaccine targeting a broader spectrum of pneumococci is warranted.
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Isolation, antigenicity and immunogenicity of Lleida bat lyssavirus
The lyssaviruses are an important group of viruses that cause a fatal encephalitis termed rabies. The prototypic lyssavirus, rabies virus, is predicted to cause more than 60 000 human fatalities annually. The burden of disease for the other lyssaviruses is undefined. The original reports for the recently described highly divergent Lleida bat lyssavirus were based on the detection of virus sequence alone. The successful isolation of live Lleida bat lyssavirus from the carcass of the original bat and in vitro characterization of this novel lyssavirus are described here. In addition, the ability of a human rabies vaccine to confer protective immunity following challenge with this divergent lyssavirus was assessed. Two different doses of Lleida bat lyssavirus were used to challenge vaccinated or naïve mice: a high dose of 100 focus-forming units (f.f.u.) 30 µl−1 and a 100-fold dilution of this dose, 1 f.f.u. 30 µl−1. Although all naïve control mice succumbed to the 100 f.f.u. 30 µl−1 challenge, 42 % (n=5/12) of those infected intracerebrally with 1 f.f.u. 30 µl−1 survived the challenge. In the high-challenge-dose group, 42 % of the vaccinated mice survived the challenge (n=5/12), whilst at the lower challenge dose, 33 % (n=4/12) survived to the end of the experiment. Interestingly, a high proportion of mice demonstrated a measurable virus-neutralizing antibody response, demonstrating that neutralizing antibody titres do not necessarily correlate with the outcome of infection via the intracerebral route. Assessing the ability of existing rabies vaccines to protect against novel divergent lyssaviruses is important for the development of future public health strategies.
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Icelandic ovine Mycoplasma ovipneumoniae are variable bacteria that induce limited immune responses in vitro and in vivo
More LessPurpose. Mycoplasma ovipneumoniae is a pathogen that causes atypical pneumoniae in sheep and goats. While infection of lambs can induce strong immune responses, typically measured as serum antibodies, experimental vaccines appear to induce lower antibody titres. The purpose of this study was to better understand the bacterium and its interaction with the host, in order to improve the vaccination strategy.
Methodology. We designed primers to compare seven M. ovipneumoniae gene sequences, in addition to the 16S sequence typically used, to estimate the variability between isolates. In addition, we labelled bacteria with a two-step process to examine whether bacteria could be intracellular as well as on the host surface in vitro. Finally, we vaccinated sheep four times and examined the induction of humoral and cellular responses.
Results. We were able to reliably amplify the seven housekeeping gene sequences to examine variability of the different isolates, and the bacteria could be found intracellularly, as well as on the host cell surface. Four vaccinations of sheep produced only modest humoral and cellular responses in this study, likely due to previous exposure of the animals to mycoplasmas.
Conclusions. The moderate immune responses seen in this study indicate that previous exposure to mycoplasmas is a challenge for vaccination of lambs against M. ovipneumoniae. However, an alternative vaccination strategy, e.g. utilizing a recombinant vaccine, may overcome this vaccination hurdle in endemic regions and we suggest a possible vaccine candidate.
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Intranasal coinfection model allows for assessment of protein vaccines against nontypeable Haemophilus influenzae in mice
Purpose. Nontypeable Haemophilus influenzae (NTHi) is a commensal in the human nasopharynx and the cause of pneumonia, meningitis, sinusitis, acute exacerbations of chronic obstructive pulmonary disease and acute otitis media (AOM). AOM is the most common ailment for which antibiotics are prescribed in the United States. With the emergence of new strains of antibiotic-resistant bacteria, finding an effective and broad coverage vaccine to protect against AOM-causing pathogens has become a priority. Mouse models are a cost-effective and efficient way to help determine vaccine efficacy. Here, we describe an NTHi AOM model in C57BL/6J mice, which also utilizes a mouse-adapted H1N1 influenza virus to mimic human coinfection.
Methodology. We tested our coinfection model using a protein vaccine formulation containing protein D, a well-studied NTHi vaccine candidate that can be found in the 10-valent Streptococcus pneumoniae conjugate vaccine. We verified the usefulness of our mouse model by comparing bacterial loads in the nose and ear between protein D-vaccinated and control mice.
Results. While there was no measurable difference in nasal bacterial loads, we did detect significant differences in the bacterial loads of ear washes and ear bullae between vaccinated and control mice.
Conclusion. The results from this study suggest that our NTHi AOM coinfection model is useful for assessing protein vaccines.
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Identification of a novel linear B-cell epitope as a vaccine candidate in the N2N3 subdomain of Staphylococcus aureus fibronectin-binding protein A
Purpose. To explore an epitope-based vaccine against Staphylococcus aureus, we screened the epitopes in the N2N3 subdomain of fibronectin-binding protein A (FnBPA) as a surface component of S. aureus.
Methodology. We expressed N2N3 proteins and prepared monoclonal antibodies (mAbs) against N2N3 by the hybridoma technique, before screening the B-cell epitopes in N2N3 using a phage-displayed random 12-mer peptide library with these mAbs against N2N3. Finally, we analysed the characters of the screened epitopes using immunofluorescence and an S. aureus infection assay.
Results. In this paper, we identified a linear B-cell epitope in N2N3 through screening a phage-displayed peptide library with a 3C3 mAb against the N2N3. The 3C3 mAb recognized the 159IETFNKANNRFSH171 sequence of the N2N3 subdomain. Subsequently, site-directed mutagenic analysis demonstrated that residues F162, K164, N167, R168 and F169 formed the core of 159IETFNKANNRFSH171, and this core motif was the minimal determinant of the B-cell epitope recognized by the 3C3 mAb. The epitope 159IETFNKANNRFSH171 showed high homology among different S. aureus strains. Moreover, this epitope was exposed on the surface of the S. aureus by using an enzyme-linked immunosorbent assay (ELISA) assay and an indirect immunofluorescence assay. As expected, the epitope peptide evoked a protective immune response against S. aureus infection in immunized mice.
Conclusion. We identified a novel linear B-cell epitope, 159IETFNKANNRFSH171, in the N2N3 subdomain of S. aureus fibronectin-binding protein A that is recognized by 3C3 mAb, which will contribute to the further study of an epitope-based vaccine candidate against S. aureus.
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