Current Clinical Trials Protocols and the Global Effort for Immunization against SARS-CoV-2

Abstract

Coronavirus disease 2019 (COVID-19) is the biggest health challenge of the 21st century, affecting millions of people globally. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ignited an unprecedented effort from the scientific community in the development of new vaccines on different platforms due to the absence of a broad and effective treatment for COVID-19 or prevention strategy for SARS-CoV-2 dissemination. Based on 50 current studies selected from the main clinical trial databases, this systematic review summarizes the global race for vaccine development against COVID-19. For each study, the main intervention characteristics, the design used, and the local or global center partnerships created are highlighted. Most vaccine developments have taken place in Asia, using a viral vector method. Two purified inactivated SARS-CoV-2 vaccine candidates, an mRNA-based vaccine mRNA1273, and the chimpanzee adenoviral vaccine ChAdOx1 are currently in phase III clinical trials in the respective countries Brazil, the United Arab Emirates, the USA, and the United Kingdom. These vaccines are being developed based on a quickly formed network of collaboration.

Keywords: COVID-19; D); SARS-CoV-2; immunization; research and development (R& vaccine.

Figure 1

Over-time distribution of multiplatform vaccine clinical trials according to the study phase. (A) Clinical trial protocols beginning in each month classified by the phase of development. (B) Cumulative analysis of clinical trial phases over the months.

Figure 2

Clinical trial protocols multiplatform distribution for the development of vaccine candidates based on nucleic acid platforms (blue colors) comprising RNA and DNA vaccines, non-replicating viral vectors (red), inactivated SARS-CoV-2 (pink), protein subunits (light green), virus-like particles (dark green), dendritic cells (purple), and artificial antigen presentation cells modified by lentiviral vector (orange). Abbreviations: VLP: Virus-like particle; aAPC: artificial antigen presentation cells; LMV: lentiviral modified vector.

Figure 3

Timing clinical trial progress analysis by the phase of study of each clinical trial protocol for active immunization against COVID-19 (vaccine) and the timing progress rate (TPR) according to the initiation and completion date of each study. Note: * the NCT04324606 clinical trial protocol was also registered in the European database for clinical studies with the following identification: EudraCT 2020-001072-15.

Figure 4

Study design of vaccine clinical trials against COVID-19 distributed inside out by the different types of allocation, masking, estimated enrollment, rehearsal center, and study countries. The color scale bar represents the number of volunteers estimated in each protocol. Abbreviations: NR—not reported; UK—the United Kingdom; USA—the United States of America.

Figure 5

The global distribution of clinical trials by phase (circles) that are developing research on vaccines against COVID-19 (red bar) in the world and their recruitment centers (cylinder). This map displays only the centers that had more than 5 recruitment centers. In particular, the main centers of each continent are arranged around the central map. Phase I (red circle), phase I-II (red-blue circle), phase II (blue circle), phase II-III (green-blue circle), and phase III (green circle).

Figure 6

Clinical trial distribution by country/continent and phase. (A): CTPs at phase I; (B): CTPs at phase I-II; (C): CTPs at phase II; (D): CTPs at phase II-III; and (E): CTPs at phase III.