Immunogenicity and structural efficacy of P41 of Plasmodium sp. as potential cross-species blood-stage malaria vaccine.

Vaccine based strategies offer a promising future in malaria control by generating protective immunity against natural infection. However, vaccine development is hindered by the Plasmodium sp. genetic diversity. Previously, we have shown P41 protein from 6-Cysteine shared by Plasmodium sp. and could be used for cross-species anti-malaria vaccines. Two different approaches, ancestral, and consensus sequence, could produce a single target for all human-infecting Plasmodium. In this study, we investigated the efficacy of ancestral and consensus of P41 protein. Phylogenetic and time tree reconstruction was conducted by RAXML and BEAST2 package to determine the relationship of known P41 sequences. Ancestral and consensus sequences were reconstructed by the GRASP server and Unipro Ugene software, respectively. The structural prediction was made using the Psipred and Rosetta program. The protein characteristic was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the immunogenicity score for B-cell, T-cell, and MHC was determined using an immunoinformatic approach. The result suggests that ancestral and consensus have a distinct protein characteristic with high immunogenicity scores for all immune cells. We found one shared conserved epitope with phosphorylation modification from the ancestral sequence to target the cross-species vaccine. Thus, this study provides detailed insight into P41 efficacy for the cross-species anti-malaria blood-stage vaccine.

Modulation of natural killer cell functions by interactions between 2B4 and CD48 in cis and in trans.

SLAM-related receptors (SRRs) are important modulators of immune cell function. While most SRRs are homophilic, 2B4 (CD244) interacts with CD48, a GPI-anchored protein expressed on many haematopoietic cells. Here we show that natural killer (NK) cell-expressed 2B4 not only binds in trans to CD48 on neighbouring cells but also interacts in cis with CD48 on the same cell. 2B4 uses the same binding site to interact with CD48 in cis and in trans and structural flexibility of 2B4 is necessary for the cis interaction. Furthermore, the cis interaction is sufficient to induce basal phosphorylation of 2B4. However, cis interaction reduces the ability of 2B4 to bind CD48 in trans As a consequence, stimulation-dependent phosphorylation of 2B4 upon binding to CD48 positive target cells is reduced. Interfering with the cis interaction therefore enhanced the lysis of CD48-expressing tumour cells. These data show that the density of 2B4 and CD48 on both the NK cell and the potential target cell modulates NK cell activity.