Gene-encoded nanoparticle vaccine platforms for in vivo assembly of multimeric antigen to promote adaptive immunity

Abstract

Nanoparticle vaccines are a diverse category of vaccines for the prophylaxis or treatment of various diseases. Several strategies have been employed for their optimization, especially to enhance vaccine immunogenicity and generate potent B-cell responses. Two major modalities utilized for particulate antigen vaccines include using nanoscale structures for antigen delivery and nanoparticles that are themselves vaccines due to antigen display or scaffolding-the latter of which we will define as "nanovaccines." Multimeric antigen display has a variety of immunological benefits compared to monomeric vaccines mediated through potentiating antigen-presenting cell presentation and enhancing antigen-specific B-cell responses through B-cell activation. The majority of nanovaccine assembly is done in vitro using cell lines. However, in vivo assembly of scaffolded vaccines potentiated using nucleic acids or viral vectors is a burgeoning modality of nanovaccine delivery. Several advantages to in vivo assembly exist, including lower costs of production, fewer production barriers, as well as more rapid development of novel vaccine candidates for emerging diseases such as SARS-CoV-2. This review will characterize the methods for de novo assembly of nanovaccines in the host using methods of gene delivery including nucleic acid and viral vectored vaccines. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Keywords: antigen scaffolding; de novo assembly; nanoparticle vaccines; nucleic acid vaccines; viral vectored vaccines.

FIGURE 1

Mechanism of action for in vivo assembling nanovaccines. Depending on the delivery vector, nanovaccines undergo different in vivo assembly processes, involving transcription and subsequent mRNA translocation or direct RNA translation. DNA plasmid transfection involves translocation into the nucleus, transcription of the plasmid, and processing and translation of the resultant mRNA in the cytoplasm. Viral vectors, such as an adenovirus vector, deposit the viral genome into the nucleus. RNA vaccines do not require translocation to the nucleus; translation of the mRNA transcript occurs in the cytoplasm. Antigen can be processed or presented by the target cell on MHC Class I (1). Additionally, antigen can be assembled and secreted by target cells and drain to local lymph nodes (2). Trafficking of antigen can also be mediated by antigen-presenting cells (APCs). APC uptake of antigen can be mediated through apoptotic bodies or direct uptake of soluble antigen and subsequently trafficked to draining lymph nodes (3). In addition, APCs themselves can be directly targeted, transfected, or transduced and subsequently display antigen and traffic to draining lymph nodes (4). Within local draining lymph nodes, immune presentation occurs. Attributes of nanovaccines allow for potent B-cell activation within germinal centers as well as enhanced APC cross-presentation, allowing for increased CD8+ T-cell activity. Created with Biorender.com.