INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-Coronavirus (SARS-CoV-2) in Wuhan, China. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global Coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review was to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a-priori protocol registration with PROSPERO (181483), systematic research of the published literature was conducted on April 24, 2020, using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database to identify relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA Guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 preprint articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.