The invention provides peptides derived from a ubiquitous protein, and nucleic acids encoding such peptides. The invention extends to various uses of these peptides and nucleic acids, for example, as antigens for use in vaccines per se and in the generation of antibodies for use in therapeutic drugs for the prevention, amelioration or treatment of infections caused by sepsis-inducing bacteria. The invention particularly benefits immunocompromised hosts such as neonates, babies, children, women of fertile age, pregnant women, foetuses, the elderly and diabetics.

The invention provides peptides derived from a ubiquitous protein, and nucleic acids encoding such peptides. The invention extends to various uses of these peptides and nucleic acids, for example, as antigens for use in vaccines per se and in the generation of antibodies for use in therapeutic drugs for the prevention, amelioration or treatment of infections caused by sepsis-inducing bacteria. The invention particularly benefits immunocompromised hosts such as neonates, babies, children, women of fertile age, pregnant women, foetuses, the elderly and diabetics.

The invention provides in part methods of treating cancers of a specific organ or tissue by administering a composition that is antigenically specific for one or more microbes that are pathogenic in the specific organ or tissue in which the cancer is situated.

The present invention provides methods and systems for targeted delivery of a compound to a target cell that over-expresses two different proteinases. Specifically, two different modified protective antigen proteins, each comprising a cleavage site recognized by a distinct proteinase in place of the native proteinase cleavage site recognized by furin, are administered in combination with a compound that contains a protective antigen binding site. Upon cleavage by the two proteinases the two modified protective antigen proteins form a hetero-oligomer, allowing the compound to bind to the hetero-oligomer and subsequently to be translocated into the target cell.

The present invention provides methods and systems for targeted delivery of a compound to a target cell that over-expresses two different proteinases. Specifically, two different modified protective antigen proteins, each comprising a cleavage site recognized by a distinct proteinase in place of the native proteinase cleavage site recognized by furin, are administered in combination with a compound that contains a protective antigen binding site. Upon cleavage by the two proteinases the two modified protective antigen proteins form a hetero-oligomer, allowing the compound to bind to the hetero-oligomer and subsequently to be translocated into the target cell.

Disclosed are capsular polysaccharide (CPS)-protein immunogenic conjugates useful for providing protection against any condition or disease associated with Burkholderia pseudomallei or Burkholderia mallei, such as melioidosis or glanders, respectively. For example, a disclosed CPS-protein immunogenic conjugate includes purified 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei chemically activated and covalently linked to recombinant CRM 197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Methods of inducing an immune response are disclosed. The methods include the use of a CPS-protein immunogenic conjugate, alone or in conjunction with other agents, such as Hcp1 and TssM, to prevent infection with B. pseudomallei or B. mallei. Also disclosed are methods for treating a subject having melioidosis or glanders.

The present invention is drawn to conjugates and vaccine compositions comprising a Pseudomonas flagellin or an antigenic fragment or derivative thereof linked to one or more Klebsiella surface polysaccharide antigens, such as Klebsiella pneumoniae O5 polysaccharide from serovars O1, O2a, O2a,c, O3, O4, O5, O7, O8 and 012. The present invention also provides serovar reagent strains to produce the conjugates and vaccine compositions and methods of inducing an immune response with the conjugates and vaccine compositions.

The present invention is drawn to conjugates and vaccine compositions comprising a Pseudomonas flagellin or an antigenic fragment or derivative thereof linked to one or more Klebsiella surface polysaccharide antigens, such as Klebsiella pneumoniae O5 polysaccharide from serovars O1, O2a, O2a,c, O3, O4, O5, O7, O8 and 012. The present invention also provides serovar reagent strains to produce the conjugates and vaccine compositions and methods of inducing an immune response with the conjugates and vaccine compositions.

A tetrasaccharide of formula I and a method of production thereof are provided. Furthermore, a conjugate comprising the tetrasaccharide and a molecule attached to the tetrasaccharide, preferably via its amine group, is also provided. Compositions, preferably immunogenic or vaccine compositions, comprising this tetrasaccharide or this conjugate are also provided. Such tetrasaccharides, conjugates, and compositions can be used for preventing or treating a disease caused by a Burkholderia infection in a subject, for inducing the production of anti-Burkholderia antibodies in a subject, or for diagnosing a Burkholderia infection in a subject. Preferably, the Burkholderia infection is an infection by Burkholderia pseudomallei (Bp) or Burkholderiamallei (Bm); the disease is melioidosis or glander; and/or the anti-Burkholderia antibodies are anti-Burkholderia pseudomallei(Bp) antibodies or anti-Burkholderia mallei (Bm)

The present invention refers to a method for the production of live attenuated bacterial strains, suitable as vaccine candidates, comprising the steps of: A. providing a bacterial strain capable of expressing glutamate racemase and possibly D-amino acid transaminase and comprising a peptidoglycan cell wall, and B. inactivating the gene or genes encoding for the glutamate racemase enzyme and, if needed, the gene or genes encoding for the enzyme D-amino acid transaminase in such way that the bacterial strain is no longer capable of expressing a functional glutamate racemase and/or a functional D-amino acid transaminase;
wherein the inactivation of said genes causes said bacterial strain to be auxotrophic for D-glutamate.