Rino Rappuoli

..Dozens of new infectious diseases are expected to emerge in the coming decades. Controlling these diseases will require a better understanding of the worldwide threat and economic burden of infectious diseases and a global agenda...

..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...

..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...

..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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..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...

..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...

..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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..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...

..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 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...

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

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

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

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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...

..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...

..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...

..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...

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

..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...

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

..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...

..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...

..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...

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

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

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

..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...

..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...

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

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..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 novel antigen is a top candidate for the development of a new vaccine against meningococcus...

..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...

..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 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...

..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...

..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...

..These studies are also needed for deciphering those aspects of the effector immune responses that correlate with protection against H. pylori infection and disease...

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

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..Immunogold electron microscopy revealed that the structures have a pilus-like form. These large structures have gone unrecognized in decades of studies of Group B Streptococcus...

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

..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...

..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...

..Interestingly, the decay of circulating antibodies is faster in mice lacking iNKT cells. These findings point to a homeostatic role for iNKT cells on critical features of the antibody response such as immunity and B cell memory...

..The Neisseria meningitidis serogroup B project, the first example of Reverse Vaccinology, as well as the application of this strategy to develop novel vaccines against other human pathogens are discussed...

..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...

..This process consisted of an active and transient opening of cell junctions. Indeed, GBS was preferentially found along the cell perimeter, where it colocalized with junctional protein complexes...

..The presence of two independently regulated fur promoters may allow meningococcus to fine-tune expression of this regulator controlling iron homeostasis, possibly during infection...

..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...

..The P(1043) and P(tlpB) promoters were demonstrated to be coordinately regulated in response to growth phase in H. pylori. The essential role of HP1043 in encoding a cell cycle regulator is discussed...

..The serine protease activity is localized at the amino-terminal domain, whereas the binding domain is in the carboxy-terminal region. The role of App in adhesion was confirmed also in N. meningitidis...

..This information is fundamental to our understanding of bacterial pathogenesis and may facilitate the design of better vaccines...

..NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages...

..In addition, we argue that innovative vaccination strategies, together with special vaccine formulations which may offer cross-protection against multiple flu pandemic strains might avert the worse effects of an influenza infection...

..Of particular interest for safer mass immunization campaigns are needle-free delivery devices, which would avoid problems due to needle re-use in many parts of the world and would avoid needle-stick injuries...

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..However, the increased cost of producing new vaccines and regulatory uncertainty remain challenges for vaccine manufacturers...

..Of particular interest for safer mass immunization are needle-free delivery devices, which would avoid problems due to needle re-use in many parts of the world, or needle-stick injuries...

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

..Importantly, intranasal but not parenteral immunization, induced bactericidal antibodies at the nasal level, when formulated with both delivery system and adjuvant...

..These results show that human ARTs possess a differential capacity to respond to bacteria cell wall components and might play a crucial role in innate immune response in airways...

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..This review focuses on some recent advances in the identification of vaccine candidates by mining the genomic sequences of pathogenic bacteria...

..Although work on the 'easy' vaccines has already been completed, it is hoped that a combination of conceptual and technical innovation will enable the development of more complex and sophisticated vaccines in the future...

..The data indicate that the m2 m-region was acquired and spread through the population by horizontal transfer of DNA...

..Given that the number of unique genes is vast, the pan-genome of a bacterial species might be orders of magnitude larger than any single genome...

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..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...

..One of them, identified in Neisseria meningitidis has been extensively characterized and shown to possess the predicted enzymatic activity, suggesting a possible role of this protein in the virulence of Meningococcus...

..Innate imprinting by toxin-based immunotherapeutics may provide generic protection against infectious disease in the lung, without the need for coadministered pathogen-specific Ag...

..Microarray-generated gene expression profiling appears to be a very effective approach to define new regulons and regulatory pathways in pathogenic bacteria...

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

..Our results suggest reciprocal adjuvant effects of rBCG-FC and rBCG-CRM197, which may contribute to induction of a more effective immune response against both diseases...

..GNA2132 is thus a promising vaccine candidate for prevention of disease caused by N. meningitidis...

..Overall, these findings demonstrate that mutants of enterotoxins with reduced toxicity are effective adjuvants for transcutaneous immunization...

..This Review highlights efforts towards this goal and describes a template that can be followed to develop vaccines against other bacterial pathogens...

..Furthermore, their splenocytes proliferated and secreted IFN-gamma and IL-6 in response to Tat. Finally, CTLs were also elicited and they recognized an epitope localized within aa 11-40 of Tat...

..The fully nontoxic LTK63 mutant has now been successfully tested in human volunteers with a trivalent subunit influenza vaccine...

..However, a restricted sIgA response suggests that care must be taken in the priming-boosting strategy and clinical sampling techniques when evaluating such vaccines for the induction of local mucosal immunity...

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..These results show that it is possible to interrogate the memory repertoire of immune donors to rapidly and efficiently isolate neutralizing antibodies that have been selected in the course of natural infection...

..However, further studies are required to confirm the potential of TCI with glycoconjugate vaccines in humans...

..tb in LTK63/Ag85B-ESAT-6-boosted mice, compared with BCG-vaccinated animals. Thus, LTK63/Ag85B-ESAT-6 represents an efficient preventive vaccine against tuberculosis with a strong ability to boost prior BCG immunity...

..The N. meningitidis genome is characterized by the horizontal acquisition of multiple genetic islands; the study of these islands reveals important sets of genes varying between isolates and likely to be related to pathogenicity...

..An influenza vaccine made as a simple particulate formulation of inactivated virus, and given repeatedly onto the nasal mucosa, may thus be an attractive alternative to currently available vaccines...

..Thus, we have identified novel, unmodified protein ligands for SR-A that are able to inhibit meningococcal interactions with macrophages in vitro...