Frequent and high-load manual material handling (MMH) tasks often cause back injuries to the workers, and backsupport exoskeletons are developed for individuals with MMH tasks. However, these exoskeletons usually cannot adapt well to the movements of the wearer's spine. This paper introduces a new bio-inspired 5-DOF origami, and via mechanical design, a unique rigid-flexible coupled bio-inspired origami mechanism is proposed. This origami mechanism is compact and lightweight, and it has stable kinematic behaviors. With the designed origami mechanisms, a novel active origami-based robotic spine assistive exoskeleton (OSAE) is developed to assist individuals with MMH tasks during the symmetric and asymmetric lifting. The OSAE is actuated by a cable-driven module through an under-actuated spine module that consists of seven origami mechanisms. With the designed spine module, the OSAE can adapt well to the wearer's spine motions during MMH tasks. Modeling of the 5- DOF origami is described, and an adaptive control strategy is proposed for the exoskeleton to adapt to different lifting methods and objects with different weights. The experimental results demonstrate the effectiveness of the proposed OSAE. During the symmetric lifting of a 10-kg object, a reduction of 41.28% of the average muscle activity of the wearer's lumbar erector spinae muscle (LES) is observed, and reductions of 30.15% and 39.54% of the average muscle activities of the wearer's left and right LES are observed, respectively, during the asymmetric lifting of a 10- kg object.