Nano-Enabled COVID-19 Vaccines: Meeting the Challenges of Durable Antibody Plus Cellular Immunity and Immune Escape

Nel, André E.; Miller, Jeff F.

[Image: see text] At the time of preparing this Perspective, large-scale vaccination for COVID-19 is in progress, aiming to bring the pandemic under control through vaccine-induced herd immunity. Not only does this vaccination effort represent an unprecedented scientific and technological breakthrough, moving us from the rapid analysis of viral genomes to design, manufacture, clinical trial testing, and use authorization within the time frame of less than a year, but it also highlights rapid progress in the implementation of nanotechnology to assist vaccine development. These advances enable us to deliver nucleic acid and conformation-stabilized subunit vaccines to regional lymph nodes, with the ability to trigger effective humoral and cellular immunity that prevents viral infection or controls disease severity. In addition to a brief description of the design features of unique cationic lipid and virus-mimicking nanoparticles for accomplishing spike protein delivery and presentation by the cognate immune system, we also discuss the importance of adjuvancy and design features to promote cooperative B- and T-cell interactions in lymph node germinal centers, including the use of epitope-based vaccines. Although current vaccine efforts have demonstrated short-term efficacy and vaccine safety, key issues are now vaccine durability and adaptability against viral variants. We present a forward-looking perspective of how vaccine design can be adapted to improve durability of the immune response and vaccine adaptation to overcome immune escape by viral variants. Finally, we consider the impact of nano-enabled approaches in the development of COVID-19 vaccines for improved vaccine design against other infectious agents, including pathogens that may lead to future pandemics.