In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

International audiencePSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in severalLeishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice.We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in aL. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L.braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals weresubdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantuminfection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high orlow levels of IFN-c in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detectedin sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-c, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-a in more. No significant cytokine response wasobserved in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increasein CD4+ T cells producing IFN-c after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between thepercentage of IFN-c-producing CD4+ T cells and the released IFN-c. We showed that the LaPSA-38S protein was able toinduce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infectionindicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacityof Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infectio

El antígeno de superficie PSA de Leishmania infantum: un nuevo miembro de la familia de proteínas con repeticiones ricas en leucinas

El antígeno PSA de Leishmania infantum presenta una elevada homología en su estructura primaria con los antígenos PSA-2 de Leishmania major y GP461M2 de Leishmania amazonensis. El análisis de su secuencia de aminoácidos indica que el 60% de la molécula está constituida por 13 motivos repetidos con una longitud que oscila entre los 24 y 25 residuos. La secuencia consenso obtenida para estos motivos concuerda con la secuencia consenso descrita para los motivos repetidos ricos en leucinas, por lo que tanto la PSA de L. infantum como la PSA-2 de L. major y la GP461 M2 de L. amazonensis pueden ser clasificados como nuevos miembros de la familia de proteínas con repeticiones ricas en leucinas. La proteína recombinante y especialmente sus fragmentos expresados de forma independiente son reconocidos eficazmente por sueros obtenidos a partir de perros infectados por el parásito y de pacientes humanos con leishmaniasis.The primary structure of the PSA antigen from Leishmania infantum shows a high homology with Leishmania major PSA-2 antigen and Leishmania amazonensis GP46/M2 antigen. Aminoacid sequence anaIysis indicates that 60% of the molecule is formed by 13 repeated motives 24-25 aminoacids in length. The consensus sequence derived from these motives shows a highly significant homology with the consensus sequence described for leucine rich repeats, which indicates that L. infantum PSA, L. major PSA-2 and L. amazonensis GP46/M2 may be included into the newly described family of leucine rich repeat containing proteins. The expressed recombinant protein and severa!. fragments expressed individually are efficiently recognized by sera from L. infantum naturally infected dogs and leishmaniasic human patients

Leishmania infantum PSA surface antigen: a new member of the family of leucine rich repeat containing proteins

El antígeno PSA de Leishmania infantum presenta una elevada homología en su estructura primaria con los antígenos PSA-2 de Leishmania major y GP461M2 de Leishmania amazonensis. El análisis de su secuencia de aminoácidos indica que el 60% de la molécula está constituida por 13 motivos repetidos con una longitud que oscila entre los 24 y 25 residuos. La secuencia consenso obtenida para estos motivos concuerda con la secuencia consenso descrita para los motivos repetidos ricos en leucinas, por lo que tanto la PSA de L. infantum como la PSA-2 de L. major y la GP461 M2 de L. amazonensis pueden ser clasificados como nuevos miembros de la familia de proteínas con repeticiones ricas en leucinas. La proteína recombinante y especialmente sus fragmentos expresados de forma independiente son reconocidos eficazmente por sueros obtenidos a partir de perros infectados por el parásito y de pacientes humanos con leishmaniasis.The primary structure of the PSA antigen from Leishmania infantum shows a high homology with Leishmania major PSA-2 antigen and Leishmania amazonensis GP46/M2 antigen. Aminoacid sequence anaIysis indicates that 60%  of the molecule is formed by 13 repeated motives 24-25 aminoacids in length. The consensus sequence derived from these motives shows a highly significant homology with the consensus sequence described for leucine rich repeats, which indicates that L. infantum PSA, L. major PSA-2 and L. amazonensis GP46/M2 may be included into the newly described family of leucine rich repeat containing proteins. The expressed recombinant protein and severa!. fragments expressed individually are efficiently recognized by sera from L. infantum naturally infected dogs and leishmaniasic human patients

Consensus and controversies in the definition, assessment, treatment and monitoring of BTcP: results of a Delphi study.

There is no unanimous consensus on the clinical features to define breakthrough cancer pain (BTcP). The current project aimed to investigate the opinion of a panel of experts on cancer pain on how to define, diagnose, assess, treat and monitor BTcP. A two-round Spanish multi-centre exploratory Delphi study was conducted with medical experts (n = 90) previously selected from Medical Oncology Services, Radiation Oncology, Palliative Care/Home Care Teams, and Pain Units. The study intended to seek experts' consensus and to define a set of recommendations for the management of BTcP. It was generally agreed that, definition of BTcP implies that baseline pain should be controlled (84 %), although not necessarily with opioids (only 30 %); there must be exacerbations (98.9 %); the duration of each episode should last The present Delphi study identified a set of recommendations to define, assess and monitor BTcP