Rino Rappuoli

..Here, we review the options available in the short term and also briefly address the solutions that research may make available in the long term...

..New and challenging targets for conjugate vaccines are represented by cancer and other non-infectious diseases...

..The European Commission-sponsored Advanced Immunization Technologies project--ADITEC--brings together some of the leading laboratories in the field to tackle the problems that no lab can tackle in isolation...

..Supported by the innovations derived from new technologies, vaccines will address the new needs of a twenty-first century society characterized by increased life expectancy, emerging infections and poverty in low-income countries...

..Streptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group...

..The lessons learned from the 2009 H1N1 pandemic are of paramount importance to develop more effective preparations against future pandemics...

..We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines...

..However, for this to happen, we need to increase the public trust in vaccination so that vaccines can be perceived as the best insurance against most diseases across all ages...

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..All together, these data suggest that the newly identified surface exposed protein Ng-OmpA represents a novel virulence factor of gonococcus...

..Multigenome analysis and screening described here represent a powerful strategy for identifying potential vaccine candidates against highly variable pathogens...

..Thus, pneumococci encode at least two types of pili that play a role in the initial host cell contact to the respiratory tract and are potential antigens for inclusion in a new generation of pneumococcal vaccines...

..We suggest that CD4(+) T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines...

..Taken together, these data show that the N19 polyepitope represents a strong and valid option for the generation of improved or new combined glycoconjugate vaccines...

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..These data could affect the design of efficacious mucosal vaccines and their safety...

..Our data suggest that LTK63 acts as an airway infection mimic that establishes a generic protective environment limiting respiratory infection by innate immune mechanisms and by improving adaptive responses to invading pathogens...

..Collectively, our results underline a putative role of NhhA in meningococcal pathogenesis and ascertain its structural and functional belonging to the emerging group of bacterial autotransporter adhesins with trimeric architecture...

..Taken together, our results suggest that SrtA is a good candidate for inclusion in a multicomponent, protein-based, pneumococcal vaccine...

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..Combining the structural and functional data, a model emerges where the pilus RrgB backbone serves as a carrier for surface located adhesive clusters of RrgA that facilitates the interaction with the host...

..A lot of work must be done, but deciphering the information provided by genome sequences and using it to better understand the host-pathogen interactions has proved to be the key for protection...

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..These data give new insights on the structure-function relationship of oligomeric coiled-coil adhesins and suggest a potential role of this protein in the pathogenesis of BPF...

..We conclude that GNA2132 is an important protective antigen of N. meningitidis and we propose to rename it, Neisserial Heparin Binding Antigen (NHBA)...

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..The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood...

..We demonstrate that the structure-based design of multiple immunodominant antigenic surfaces on a single protein scaffold is possible and represents an effective way to create broadly protective vaccines...

..These results suggest that a vaccine composed of RrgB321 has the potential to cover 30% or more of all pneumococcal strains and support the inclusion of this fusion protein in a multicomponent vaccine against S. pneumoniae...

..Limited data are available on the prevalence of the rlrA operon in pneumococci; therefore, we investigated its distribution and its antigenic variation among disease-causing strains...

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..Both active and passive immunization with recombinant pilus subunits afforded protection against lethal challenge with the S. pneumoniae serotype 4 strain TIGR4...

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..Altogether our data suggest that the mechanism of regulation of NadR by 4-HPA mainly involves the stabilization of the dimer in a configuration incompatible with DNA binding...

..Finally, the importance of an interconnection between metal-responsive gene networks for homeostasis is discussed...

..Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response...

..Our structural analyses provide the first direct experimental evidence that the native S. pneumoniae pilus shaft is composed exclusively of covalently linked monomeric RrgB subunits oriented head-to-tail...

..These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains...

..This assay allows typing of large panels of strains and prediction of coverage of protein-based meningococcal vaccines. Similar assays may be used for protein-based vaccines against other bacteria...

..Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety...

..Sequencing each gene in the different strains will be important to evaluate antigen conservation and assortment and to allow a future prediction of potential vaccine coverage...

..The practical consequence is that, in many cases, a universal vaccine is possible only by including a combination of antigens and this combination must take into account the pathogen population structure...

..When present, the gene is 100% conserved in sequence and is inserted upstream of and co-transcribed with the lipoamide dehydrogenase E3 gene. Possible roles in the pathogenesis of N. meningitidis are discussed...

..NadA is likely to improve the fitness of N. meningitidis contributing to the increased virulence of strains that belong to the hypervirulent lineages...

..In addition, we describe the potential of these powerful technologies in understanding the pathogenesis of various bacteria...

..Our results indicated that the enterobactin binding site was distinct from the site involved in binding to human factor H and stimulates new hypotheses about possible multiple activities of fHbp...

..This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism...

..Finally, we present a discussion to situate omics-guided rational vaccine design in the broader context of global public health and how it can benefit citizens in both developed and developing countries...

..In this review, we describe how genomic approaches can be used to identify novel vaccine candidates or create safer live-attenuated vaccines...

..We began to dissect the regulatory networks of Fur and the heat shock (stress) response in N. meningitidis, and the observed interlink between the two circuits is discussed...

..N19-based conjugates are superior to CRM-based conjugates to induce protective immune responses to MenC conjugates...

..In conclusion, antisqualene antibodies are not increased by immunization with vaccines with the MF59 adjuvant. These data extend the safety profile of the MF59 emulsion adjuvant...

..The presence of NadA can therefore be used as a tool to study the dynamics of meningococcal infections and understand why this bacterium, which is mostly a commensal, can become a severe pathogen...

..The vaccine given without adjuvant significantly reduced viral load in the lungs but did not protect from infection. Only the vaccine with adjuvant completely prevented both pulmonary and nasal infection...

..The concept of "Reverse Vaccinology" can be easily applied to all the pathogens for which vaccines are not yet available and can be extended to parasites and viruses...

..We show that Ng-MIP promotes the intracellular survival of N. gonorrhoeae in macrophages, highlighting a possible role of this protein in promoting the persistence of gonococcal infection...

..Deletion of the upstream operator in the norB promoter abolished activation of transcription in vivo in response to iron and in vitro in response to Fur. The role of such a dual mechanism of Fur regulation during infection is discussed...

..In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens...

..These data shed light on the different components of the immune response to the 2009 H1N1 pandemic influenza vaccination and may have implications in the design of vaccination strategies against future influenza pandemics...

..Altogether our results show that variation of host Hsp90 expression or activity interferes with adhesive and invasive events driven by NadA...

..The gene encoding the most protective antigen was detected in most of the E. coli isolates, highly conserved in sequence and found to be exported by a type II secretion system which seems to be nonfunctional in nonpathogenic strains...

..This article will provide examples of how public-private partnerships both in developed and developing countries have been established to handle specific problems concerning vaccination...

..The implications of these findings for the elucidation of the networks regulating heat shock gene expression in H. pylori are discussed...

..Overall, the conventional empiric approach to vaccine development is being replaced by vaccine design. The recent development of synthetic genomics may provide a further opportunity to design vaccines...

..This is the first observation suggesting that a member of the ADP-ribosyltransferase family contains an Fe-S cluster implicated in catalysis. This observation may unravel novel functions exerted by this class of enzymes...

..The genomic revolution has had a dramatic effect on our ability to find new vaccine targets and develop effective vaccines...

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..A lot of work must be done, but deciphering the information provided by genome sequences and using it to better understand the host-pathogen interactions has proved to be the key for protection...

..Ultimately, the identification of immunogenic surface antigens and assessment of their efficacy will be imperative in the development of a vaccine with the ability to protect against invasive disease independent of serotype...

..Arginine in position 204 was identified as important for binding of the monoclonal antibody. The identification of the region containing bactericidal epitopes is an important step in the design of new vaccines against meningococci...

..The role of CrgA in the regulation of gene expression during the infectious cycle of N. meningitidis is discussed...

..We propose that its role is ensuring that Fur expression is not repressed below a minimum threshold level. Our data supports a novel promoter architecture and mechanism of regulation by Fur...

..We will also discuss how extending clinical investigation to events occurring early after vaccination can help identify early predictive markers of protective memory and thus contribute to faster development of better and safer vaccines...

..fHbp is important for survival in human blood, human sera, and in presence of antimicrobial peptides, independently of its expression level. All these properties make fHbp a unique vaccine antigen...

..This ever-growing body of genomic data and new genome-based approaches will play a critical role in the future to enable timely development of vaccines and therapeutics to control emerging infectious diseases...

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..These results demonstrate that the concomitant use of chitosan microparticles and the LTK63 mutant significantly enhances the immunogenicity and the protective efficacy of vaccines given intranasally...

..These results suggest that the structure of the H. pylori secretion apparatus itself is involved in this process...

..We conclude that MF59-adjuvanted vaccines confer protection also against influenza virus strains which are not fully matched with those included in the vaccine...

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..Because MF59 did not activate any of the Toll-like receptors in vitro, we propose that MF59 requires MyD88 for a Toll-like receptor-independent signaling pathway...

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..The MF59 adjuvant broadens the distribution of B-cell epitopes recognized on HA and NA following immunization...

..These data show that vaccination against this pathogen is feasible. More research is required to understand the immunological mechanisms underlying immune-mediate protection...

..Serum bactericidal antibody titers against selected bacteria were within assay variability through a selection event frequency of 1 in 10(-5). No change in antigen expression was observed by Western blotting...

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..Additional clinical applications of CRM(197), as in chemotherapy, also exist...

..The modulation of gene expression via the ModD phase-variable regulon (phasevarion), and its significant association with the cc41/44, suggest a role in the fitness and/or pathogenesis of strains belonging to the cc41/44...

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..Surprisingly, these three studies reported conflicting results on the requirement of the Nlrp3 inflammasome complex for alum adjuvant effects in vivo. This commentary attempts to resolve some of these discrepancies...

..Understanding the structural basis for immunogenicity and immunodominance will allow us to improve vaccine efficacy and broaden the range of vaccine-preventable diseases...

..A more thorough understanding of the kinetics of these receptin interactions could provide a new approach to preventing deeper tissue invasion in H. pylori infections and could represent an alternative to antibiotic treatment...

..Cytochalasin D significantly impaired this antibacterial activity, suggesting that phagocytosis plays a major role in the antibody-mediated H. pylori killing...

..We conclude that GNA33 is a highly conserved lipoprotein which plays an important role in peptidoglycan metabolism, cell separation, membrane architecture, and virulence...

..Thus, CagA translocation followed by tyrosine phosphorylation at the EPIYA motifs promotes a growth factor-like response with intense cytoskeletal rearrangements, cell elongation effects and increased cellular motility...

..It is absorbed on aluminum hydroxide or aluminum phosphate. Thus, new molecules are available to improve the immune response to vaccines also in humans: this is the beginning of a new era in vaccinology...

..Overall, the PPN assay represents a valid alternative to conventional serological methods for the evaluation of H5N1 vaccine immunogenicity...