A review of malaria vaccine clinical projects based on the WHO rainbow table

Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below.     

Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.     

Personality,Relationship Conflict,and Teamwork-Related Mental Models

This study seeks to explore whether neuroticism, agreeableness, and conscientiousness moderate the influence of relationship conflict experienced in groups on changes in group members'' evaluative cognitions related to teamwork quality (teamwork-related mental models). Data from 216 students, nested in 48 groups were analyzed using a multilevel modeling approach. Our results show that the experience of relationship conflict leads to a negative shift from the pre-task to the post-task teamwork-related mental models. Moreover, the results indicate that conscientiousness buffered the negative association between relationship conflict and the change in teamwork-related mental models. Our results did not support the hypothesized moderating effect of agreeableness and show that the detrimental effect of relationship conflict on the shift in teamwork-related mental models is accentuated for group members scoring low rather than high on neuroticism. These findings open new research venues for exploring the association between personality, coping styles and change in teamwork-related mental models.     

165 Protein domains: a thermodynamic definition

Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earlier crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous thermodynamically based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, domains are equated to chain segments that retain full cooperativity when excised from their parent structures. Implementing this approach computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property, grounded in solution thermodynamics.