Concerns and challenges in clinics-guided nanovaccines design and applications

Vaccines play a crucial role in the prevention and treatment of multiple diseases. Given the constraints of conventional vaccines, the development of nanovaccines, characterized by their superior design flexibility and controllability, has emerged as a compelling alternative. By utilizing nanotechnology, nanovaccines optimize the targeted delivery of antigens and adjuvants, augment antigen presentation, and facilitate precise modulation of immune cell responses, thereby exhibiting substantial potential for both preventive and therapeutic applications across a range of diseases. However, research on nanovaccines is currently stalled at the preclinical stage, with numerous challenges and shortcomings hindering their clinical translation. Herein, we discuss various design concepts and strategies for nanovaccines, along with their biomedical applications, with an emphasis on the challenges, future directions, and strategies of their clinical translation. We specifically highlight the core principles that need to be achieved in the preclinical development of nanovaccines, aiming to explore strategies to overcome existing challenges and promote their clinical application.