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Delivering COVID-19 vaccines with 4–6 weeks shelf life remains one of Africa’s most pressing challenges. The Africa Centres for Disease Control and Prevention (Africa CDC) leadership recognised that COVID-19 vaccines donated to many African countries were at risk of expiry considering the short shelf life on delivery in the Member States and slow vaccine uptake rates. Thus, a streamlined rapid response system, the urgent support mechanism, was developed to assist countries accelerate COVID-19 vaccine uptake. We describe the achievements and lessons learnt during implementation of the urgent support mechanism in eight African countries. An Africa CDC team was rapidly deployed to meet with the Ministry of Health of each country alerted for COVID-19 vaccine expiry and identified national implementing partners to quickly develop operational work plans and strategies to scale up the urgent use of the vaccines. The time between the initiation of alerts to the start of the implementation was typically within 2 weeks. A total of approximately 2.5 million doses of vaccines, costing $900 000, were prevented from expiration. The urgent support has also contributed to the increased COVID-19 vaccination coverage in the Member States from 16.1% at the initiation to 25.3% at the end of the urgent support. Some of the effective strategies used by the urgent support mechanism included coordination between Africa CDC and country vaccine task forces, establishment of vaccination centres, building the capacity of routine and surge health workforce, procurement and distribution of vaccine ancillaries, staff training, advocacy and sensitisation events, and use of trusted religious scriptures and community influencers to support public health messages. The urgent support mechanism demonstrated a highly optimised process and serves as a successful example for acceleration and integration of vaccination into different healthcare delivery points.