Vaccine Platforms Combining Circumsporozoite Protein and Potent Immune Modulators, rEA or EAT-2, Paradoxically Result in Opposing Immune Responses

Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS) protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd) based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI) responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA) or SLAM receptors adaptor protein (EAT-2). Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly improve the induction of malaria antigen specific adaptive immune responses in vivo

Bipolar disorders

Bipolar disorder is characterized by (hypo)manic episodes and depressive episodes which alternate with euthymic periods. It causes serious disability with poor outcome, increased suicidality risk, and significant societal costs. This chapter describes the findings of the PET/SPECT research efforts and the current ideas on the pathophysiology of bipolar disorder. First, the cerebral blood flow and cerebral metabolism findings in the prefrontal cortex, limbic system, subcortical structures, and other brain regions are discussed, followed by an overview of the corticolimbic theory of mood disorders that explains these observations. Second, the neurotransmitter studies are discussed. The serotonin transporter alterations are described, and the variation in study results is explained, followed by an overview of the results of the various dopamine receptor and transporter molecules studies, taking into account also the relation to psychosis. Third, a concise overview is given of dominant bipolar disorder pathophysiological models, proposing starting points for future molecular imaging studies. Finally, the most important conclusions are summarized, followed by remarks about the observed molecular imaging study designs specific for bipolar disorder.</p

Vaccination génique et antigénique avec la profiline de toxoplasme

Diplôme : Dr. d'Universit

Evaluation of protective effect of recombinant protein of Eimeria used as an adjuvant by nasal route against chronical toxoplasmosis in mice

International audienc

Evaluation of protective effect of recombinant protein of Eimeria used as an adjuvant by nasal route against chronical toxoplasmosis in mice

International audienc

Evaluation of protective effect of recombinant protein of Eimeria used as an adjuvant by nasal route against chronical toxoplasmosis in mice

National audienc

Protective immunity against Toxoplasma challenge in mice by coadministration of T. gondii antigens and Eimeria profilin-like protein as an adjuvant

International audienc

Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii: CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection both Lectin-like and EGF-like domains of MIC3 conferred protection

International audienc