Background: COVID-19 vaccination has faced a range of challenges from supply-side barriers such as insufficient vaccine supply and negative information environment and demand-side barriers centring on public acceptance and confidence in vaccines. This study assessed global spatiotemporal trends in demand- and supply-side barriers to vaccine uptake using COVID-19-related social media data and explored the country-level determinants of vaccine acceptance. Methods: We accessed a total of 13,093,406 tweets sent between November 2020 and March 2022 about the COVID-19 vaccine in 90 languages from 135 countries using Meltwater (a social listening platform). Based on 8,125 manually-annotated tweets, we fine-tuned multilingual deep learning models to automatically annotate all 13,093,406 tweets. We present spatial and temporal trends in four key spheres: (1) COVID-19 vaccine acceptance; (2) confidence in COVID-19 vaccines; (3) the online information environment regarding the COVID-19 vaccine; and (4) perceived supply-side barriers to COVID-19 vaccination. Using univariate and multilevel regressions, we evaluated the association between COVID-19 vaccine acceptance on Twitter and (1) country-level characteristics regarding governance, pandemic preparedness, trust, culture, social development, and population demographics; (2) country-level COVID-19 vaccine coverage; and (3) Google search trends on adverse vaccine events. Findings: COVID-19 vaccine acceptance was high among Twitter users in Southeast Asian, Eastern Mediterranean, and Western Pacific countries, including India, Indonesia, and Pakistan. In contrast, acceptance was relatively low in high-income nations like South Korea, Japan, and the Netherlands. Spatial variations were correlated with country-level governance, pandemic preparedness, public trust, culture, social development, and demographic determinants. At the country level, vaccine acceptance sentiments expressed on Twitter predicted higher vaccine coverage. We noted the declining trend of COVID-19 vaccine acceptance among global Twitter users since March 2021, which was associated with increased searches for adverse vaccine events. Interpretation: In future pandemics, new vaccines may face the potential low-level and declining trend in acceptance, like COVID-19 vaccines, and early responses are needed. Social media mining represents a promising surveillance approach to monitor vaccine acceptance and can be validated against real-world vaccine uptake data. Keywords: COVID-19, vaccine confidence, vaccine acceptance, vaccine hesitancy, social media, machine learning