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Background: RH5 is the leading vaccine candidate for the Plasmodium falciparum blood stage and has shown impact on parasite growth in the blood in a human clinical trial. RH5 binds to Ripr and CyRPA at the apical end of the invasive merozoite form, and this complex, designated RCR, is essential for entry into human erythrocytes. RH5 has advanced to human clinical trials, and the impact on parasite growth in the blood was encouraging but modest. This study assessed the potential of a protein-in-adjuvant blood stage malaria vaccine based on a combination of RH5, Ripr and CyRPA to provide improved neutralizing activity against P. falciparum in vitro., Methods: Mice were immunized with the individual RCR antigens to down select the best performing adjuvant formulation and rats were immunized with the individual RCR antigens to select the correct antigen dose. A second cohort of rats were immunized with single, double and triple antigen combinations to assess immunogenicity and parasite neutralizing activity in growth inhibition assays., Results: The DPX® platform was identified as the best performing formulation in potentiating P. falciparum inhibitory antibody responses to these antigens. The three antigens derived from RH5, Ripr and CyRPA proteins formulated with DPX induced highly inhibitory parasite neutralising antibodies. Notably, RH5 either as a single antigen or in combination with Ripr and/or CyRPA, induced inhibitory antibodies that outperformed CyRPA, Ripr., Conclusion: An RCR combination vaccine may not induce substantially improved protective immunity as compared with RH5 as a single immunogen in a clinical setting and leaves the development pathway open for other antigens to be combined with RH5 as a next generation malaria vaccine., Competing Interests: The authors LL and RR are employed, and MS was employed by IMV Inc. JC, AN and VK are employed by Leidos Life Sciences. SD is a named inventor on patent applications relating to RH5-based malaria vaccines. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Healer, Thompson, Mackwell, Browne, Seager, Ngo, Lowes, Silk, Pulido, King, Christen, Noe, Kotraiah, Masendycz, Rajagopalan, Lucas, Stanford, Soisson, Diggs, Miller, Youll, Wycherley, Draper and Cowman.)

Research in big data, informatics, and bioinformatics has grown dramatically (Andreu-Perez J, et al., 2015, IEEE Journal of Biomedical and Health Informatics 19, 1193-1208). Advances in gene sequencing technologies, surveillance systems, and electronic medical records have increased the amount of health data available. Unconventional data sources such as social media, wearable sensors, and internet search engine activity have also contributed to the influx of health data. The purpose of this study was to describe how 'big data', 'informatics', and 'bioinformatics' have been used in the animal health and veterinary medical literature and to map and chart publications using these terms through time. A scoping review methodology was used. A literature search of the terms 'big data', 'informatics', and 'bioinformatics' was conducted in the context of animal health and veterinary medicine. Relevance screening on abstract and full-text was conducted sequentially. In order for articles to be relevant, they must have used the words 'big data', 'informatics', or 'bioinformatics' in the title or abstract and full-text and have dealt with one of the major animal species encountered in veterinary medicine. Data items collected for all relevant articles included species, geographic region, first author affiliation, and journal of publication. The study level, study type, and data sources were collected for primary studies. After relevance screening, 1093 were classified. While there was a steady increase in 'bioinformatics' articles between 1995 and the end of the study period, 'informatics' articles reached their peak in 2012, then declined. The first 'big data' publication in animal health and veterinary medicine was in 2012. While few articles used the term 'big data' (n = 14), recent growth in 'big data' articles was observed. All geographic regions produced publications in 'informatics' and 'bioinformatics' while only North America, Europe, Asia, and Australia/Oceania produced publications about 'big data'. 'Bioinformatics' primary studies tended to use genetic data and tended to be conducted at the genetic level. In contrast, 'informatics' primary studies tended to use non-genetic data sources and conducted at an organismal level. The rapidly evolving definition of 'big data' may lead to avoidance of the term.

Merozoite surface protein 2 (MSP2) is an abundant glycosylphosphatidylinositol (GPI)-anchored protein of Plasmodium falciparum, which is a potential component of a malaria vaccine. As all forms of MSP2 can be categorized into two allelic families, a vaccine containing two representative forms of MSP2 may overcome the problem of diversity in this highly polymorphic protein. Monomeric recombinant MSP2 is an intrinsically unstructured protein, but its conformational properties on the merozoite surface are unknown. This question is addressed here by analyzing the 3D7 and FC27 forms of recombinant and parasite MSP2 using a panel of monoclonal antibodies raised against recombinant MSP2. The epitopes of all antibodies, mapped using both a peptide array and by nuclear magnetic resonance (NMR) spectroscopy on full-length recombinant MSP2, were shown to be linear. The antibodies revealed antigenic differences, which indicate that the conserved N- and C-terminal regions, but not the central variable region, are less accessible in the parasite antigen. This appears to be an intrinsic property of parasite MSP2 and is not dependent on interactions with other merozoite surface proteins as the loss of some conserved-region epitopes seen using the immunofluorescence assay (IFA) on parasite smears was also seen on Western blot analyses of parasite lysates. Further studies of the structural basis of these antigenic differences are required in order to optimize recombinant MSP2 constructs being evaluated as potential vaccine components.

The murine monoclonal antibody WO2 specifically binds the N-terminal region of the amyloid beta peptide (Abeta) associated with Alzheimer's disease. This region of Abeta has been shown to be the immunodominant B-cell epitope of the peptide and hence is considered to be a basis for the development of immunotherapeutic strategies against this prevalent cause of dementia. Structural studies have been undertaken in order to characterize the molecular basis for antibody recognition of this important epitope. Here, details of the crystallization and X-ray analysis of the Fab fragment of the unliganded WO2 antibody in two crystal forms and of the complexes that it forms with the truncated Abeta peptides Abeta(1-16) and Abeta(1-28) are presented. These crystals were all obtained using the hanging-drop vapour-diffusion method at 295 K. Crystals of WO2 Fab were grown in polyethylene glycol solutions containing ZnSO(4); they belonged to the orthorhombic space group P2(1)2(1)2(1) and diffracted to 1.6 A resolution. The complexes of WO2 Fab with either Abeta(1-16) or Abeta(1-28) were cocrystallized from polyethylene glycol solutions. These two complex crystals grew in the same space group, P2(1)2(1)2(1), and diffracted to 1.6 A resolution. A second crystal form of WO2 Fab was grown in the presence of the sparingly soluble Abeta(1-42) in PEG 550 MME. This second form belonged to space group P2(1) and diffracted to 1.9 A resolution.