Multivalent Pneumococcal Protein Vaccines Comprising Pneumolysoid with Epitopes/Fragments of CbpA and/or PspA Elicit Strong and Broad Protection

Chen, Austen; Mann, Beth; Gao, Geli; Heath, Richard J.; King, Janice; Maissoneuve, Jeff; Alderson, Mark R.; Tate, Andrea; Hollingshead, Susan K.; Tweten, Rodney K.; Briles, David E.; Tuomanen, Elaine; Paton, James C.

doi:10.1128/cvi.00293-15

Cited by 42 publications

(47 citation statements)

References 64 publications

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“…Pneumolysin toxoids have been evaluated as components of protein-based pneumococcal vaccines (Chen et al, 2015; Odutola et al, 2016). Since ~90% of estimated overall efficacy of currently licensed pneumococcal vaccine is due to reduced transmission within the population (Odutola et al, 2016), we tested whether immunization with PdB could block transmission among infant mice.…”

Section: Resultsmentioning

confidence: 99%

Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin

Zafar

Wang

Hamaguchi

et al. 2017

Cell Host & Microbe

114

142

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SUMMARY Host-to-host transmission is a critical step for infection. Here we studied transmission of the opportunistic pathogen Streptococcus pneumoniae in an infant mouse model. Transmission from nasally colonized pups required high levels of bacterial shedding in nasal secretions and was temporally correlated with, and dependent upon, the acute inflammatory response. Pneumolysin, a pore-forming cytotoxin and major virulence determinant, was both necessary and sufficient to promote inflammation, which increased shedding and allowed for intralitter transmission. Direct contact between pups was not required for transmission indicating the importance of an environmental reservoir. An additional in vivo effect of pneumolysin was to enhance bacterial survival outside of the host. Our findings provide experimental evidence of a microbial strategy for transit to new hosts and explain why an organism expresses a toxin that damages the host upon which it depends.

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Section: Resultsmentioning

confidence: 99%

Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin

Zafar

Wang

Hamaguchi

et al. 2017

Cell Host & Microbe

114

142

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“…PsrP promotes pneumococcal adherence to nasopharyngeal epithelial cells and lung cells and contributes to robust formation of biofilms (9,10,22,(24)(25)(26). CbpA plays a role in adherence, colonization and immune evasion from complement attack and opsonophagocytosis (9,10,27).…”

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confidence: 99%

Molecular characterization of Streptococcus pneumoniae, particularly serotype19A/ST320, which emerged in Krasnoyarsk, Russia

Протасова¹,

Wan²,

Бахарева

et al. 2017

Microbiology and Immunology

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Streptococcus pneumoniae, a common human pathogen, colonizes the nasopharynx and causes diseases including acute otitis media (AOM). Herein, pneumococcal serotype distributions in children before and after PCV7 vaccination and in patients with pneumococcal disease in Siberian Russia (Krasnoyarsk) are reported. Analyses included antimicrobial susceptibility testing, sequence typing (ST), pulsed field gel electrophoresis, virulence‐related surface protein gene (VSG) typing with novel primers and structural analysis by scanning electron microscopy. In healthy children (HC) prior to administration of PCV7, drug‐susceptible serotype23F/ST1500 was a major pneumococcal genotype. In the PCV7 trial, multidrug‐resistant serotype19A/ST320 emerged in vaccinees after PCV7, exhibiting a PCV7‐induced serotype replacement. Multidrug‐resistant serotype19A/ST320 was evident in patients with AOM. Community‐acquired pneumonia (CAP) isolates showed genetic similarities to the AOM (ST320) genotype, constituting a common non‐invasive AOM–CAP group. In contrast, meningitis isolates were more divergent. Overall, 25 ST types were identified; five (20%) of which were Krasnoyarsk‐native. Regarding VSGs, PI‐1 (rlrA/rrgB), PI‐2 (pitA/B), psrP and cbpA were present at 54.3%, 38.6%, 48.6%, and 95.7%, respectively, with two major VSG content types, PI‐1−/PI‐2−/psrP +/cbpA + and PI‐1+/PI‐2+/psrP ‐/cbpA +, being found for HC and non‐invasive diseases, respectively. A major clone of serotype19A/ST320 (PI‐1+/PI‐2+) produced the longest pneumococcal wire (pilus) structures in colonies. ST1016 (PI‐1−/PI‐2−) in HC had HEp‐2 cell‐adherent pili. These results suggest that serotype19A/ST320 and related genotypes, with the VSG content type PI‐1+/PI‐2+/psrP −/cbpA +, emerged in vaccinees after PCV7 in Siberia, accompanying diseases in non‐vaccinated children, and that some genotypes (serotypes19A/ST320 and 18/ST1016) produced novel pneumococcal structures, predicting their roles in colony formation and adherence.

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“…In recent years, different SAPN-based vaccines have been designed and evaluated against various pathogens, including Toxoplasma gondii, human immunodeficiency viruses (HIV), Plasmodium falciparum, severe acute respiratory syndrome (SARS) coronavirus [66][67][68][69][70][71]. Although Chen et al study, showed the trivalent antigen combination of YLN (protective peptide epitopes from CbpA) and L460D (fragment of PspA) as epitope vaccine elicited the strong and broad protection in diverse pneumococcal challenge models [72], but there isn't any report on the production of epitope-based SAPN vaccine against S. pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

Dorosti

Eslami

Nezafat

et al. 2019

Molecular and Cellular Probes

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A B S T R A C TStreptococcus pneumoniae is the main cause of diseases such as meningitis, pneumoniae and sepsis, especially in children and old people. Due to costly antibiotic treatment, and increasing resistance of pneumococcus, developing high-efficient protective vaccine against this pathogen is an urgent need. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in children and adult groups, but the serotype replacement of S. pneumoniae strains causes the reduction in efficacy of such vaccines. For overcoming the aforesaid drawbacks epitope-based vaccines are introduced as the relevant alternative. In our previous research, the epitope vaccine was designed based on immunodominant epitopes from PspA, CbpA antigens as cellular stimulants and PhtD, PiuA as humoral stimulants. Because the low immunogenicity is the main disadvantage of epitope vaccine, in the current study, we applied coiled-coil selfassembled structures for developing our vaccine. Recently, self-assembled peptide nanoparticles (SAPNs) have gained much attention in the field of vaccine development due to their multivalency, self-adjuvanticity, biocompatibility, and size similarity to pathogen. In this regard, the final designed vaccine is comprised of cytotoxic T lymphocytes (CTL) epitopes from PspA and CbpA, helper T lymphocytes (HTL) epitopes from PhtD and PiuA, the pentamer and trimmer oligomeric domains form 5-stranded and 3-stranded coiled-coils as self-assembled scaffold, Diphtheria toxoids (DTD) as a universal T-helper, which fused to each other with appropriate linkers. The four different arrangements based on the order of above-mentioned compartments were constructed, and each of them were modeled, and validated to find the 3D structure. The structural, physicochemical, and immunoinformatics analyses of final vaccine construct represented that our vaccine could stimulate potent immune response against S. pneumoniae; however, the potency of that should be approved via various in vivo and in vitro immunological tests.

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Multivalent Pneumococcal Protein Vaccines Comprising Pneumolysoid with Epitopes/Fragments of CbpA and/or PspA Elicit Strong and Broad Protection

Cited by 42 publications

References 64 publications

Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin

Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin

Molecular characterization of Streptococcus pneumoniae, particularly serotype19A/ST320, which emerged in Krasnoyarsk, Russia

Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

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