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WIREs Nanomed Nanobiotechnol
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Advancements in protein nanoparticle vaccine platforms to combat infectious disease

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Abstract Infectious diseases are a major threat to global human health, yet prophylactic treatment options can be limited, as safe and efficacious vaccines exist only for a fraction of all diseases. Notably, devastating diseases such as acquired immunodeficiency syndrome (AIDS) and coronavirus disease of 2019 (COVID‐19) currently do not have vaccine therapies. Conventional vaccine platforms, such as live attenuated vaccines and whole inactivated vaccines, can be difficult to manufacture, may cause severe side effects, and can potentially induce severe infection. Subunit vaccines carry far fewer safety concerns due to their inability to cause vaccine‐based infections. The applicability of protein nanoparticles (NPs) as vaccine scaffolds is promising to prevent infectious diseases, and they have been explored for a number of viral, bacterial, fungal, and parasitic diseases. Many types of protein NPs exist, including self‐assembling NPs, bacteriophage‐derived NPs, plant virus‐derived NPs, and human virus‐based vectors, and these particular categories will be covered in this review. These vaccines can elicit strong humoral and cellular immune responses against specific pathogens, as well as provide protection against infection in a number of animal models. Furthermore, published clinical trials demonstrate the promise of applying these NP vaccine platforms, which include bacteriophage‐derived NPs, in addition to multiple viral vectors that are currently used in the clinic. The continued investigations of protein NP vaccine platforms are critical to generate safer alternatives to current vaccines, advance vaccines for diseases that currently lack effective prophylactic therapies, and prepare for the rapid development of new vaccines against emerging infectious diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures
The interaction between the nanoparticle (NP) vaccines and the immune system results in immunological memory and protection against future infections. NP platforms are capable of stimulating the host immune response to generate both cellular (CD8+ T cell) and humoral (antibody) responses to the pathogen antigen(s) included in the vaccine formulation. As detailed in this review, each unique NP platform can generate antigen‐specific CD8+, CD4+, and/or antibody responses to immunization following uptake of the NP vaccine by local antigen‐presenting cells at the immunization site. These antigen‐presenting cells travel back to draining lymph tissues, where they process the nanoparticle vaccine platforms into protein peptides that are presented on MHC molecules to both CD8+ and CD4+ T cells. CD8+ T cells (green) are capable of directly killing infected cells (pink). CD4+ T cells (blue) interact with B cells (orange) to stimulate the maturation of the B cells into antibody‐secreting plasma cells (purple). The antibodies are specific to the pathogen and can neutralize their ability to infect and proliferate. The antigen‐specific cellular and/or humoral responses generated by the NP platforms will be maintained as memory cells against the pathogen, which can be quickly activated when the immunized individual encounters that specific pathogen in the future. Future infection with that specific pathogen results in a rapid and robust immune response that controls the proliferation and dissemination of the pathogen and significantly reduces disease pathology in the immunized individual
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Crystal structures of several protein NP scaffolds investigated for vaccine development. Self‐assembling, phage‐derived, and plant‐derived NPs are labeled in black, red, and blue, respectively. The inset shows TMV from the cross‐sectional view (left) and side view (right). Scale bars denote 20‐nm. NP structures were generated in ChimeraX using Protein Data Bank ID codes 1shs (sHsp), 1mfr (ferritin), 1b5s (E2), 5fmo (CPMV), 2ms2 (MS2), 1F15 (CMV), 3iyh (P22), and 6R7M (TMV)
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Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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