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Software process improvement (SPI) has been around for decades: frameworks are proposed, success factors are studied, and experiences have been reported. However, the sheer mass of concepts, approaches, and standards published over the years overwhelms practitioners as well as researchers. What is out there? Are there new trends and emerging approaches? What are open issues? Still, we struggle to answer these questions about the current state of SPI and related research. In this article, we present results from an updated systematic mapping study to shed light on the field of SPI, to develop a big picture of the state of the art, and to draw conclusions for future research directions. An analysis of 769 publications draws a big picture of SPI-related research of the past quarter-century. Our study shows a high number of solution proposals, experience reports, and secondary studies, but only few theories and models on SPI in general. In particular, standard SPI models like CMMI and ISO/IEC 15,504 are analyzed, enhanced, and evaluated for applicability in practice, but these standards are also critically discussed, e.g., from the perspective of SPI in small-to-medium-sized companies, which leads to new specialized frameworks. New and specialized frameworks account for the majority of the contributions found (approx. 38%). Furthermore, we find a growing interest in success factors (approx. 16%) to aid companies in conducting SPI and in adapting agile principles and practices for SPI (approx. 10%). Beyond these specific topics, the study results also show an increasing interest into secondary studies with the purpose of aggregating and structuring SPI-related knowledge. Finally, the present study helps directing future research by identifying under-researched topics awaiting further investigation.

Abstract Background Infections with Herpes simplex virus (HSV)-1 or -2 usually present as mild chronic recurrent disease, however in rare cases can result in life-threatening conditions with a large spectrum of pathology. Monoclonal antibody therapy has great potential especially to treat infections with virus resistant to standard therapies. HDIT101, a humanized IgG targeting HSV-1/2 gB was previously investigated in phase 2 clinical trials. The aim of this study was to develop a next-generation therapy by combining different antiviral monoclonal antibodies. Methods A lymph-node derived phage display library (LYNDAL) was screened against recombinant gB from Herpes simplex virus (HSV) -1 and HDIT102 scFv was selected for its binding characteristics using bio-layer interferometry. HDIT102 was further developed as fully human IgG and tested alone or in combination with HDIT101, a clinically tested humanized anti-HSV IgG, in vitro and in vivo. T-cell stimulating activities by antigen-presenting cells treated with IgG-HSV immune complexes were analyzed using primary human cells. To determine the epitopes, the cryo-EM structures of HDIT101 or HDIT102 Fab bound to HSV-1F as well as HSV-2G gB protein were solved at resolutions