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Review
. 2021 Mar 18;184(6):1589-1603.
doi: 10.1016/j.cell.2021.02.030.

Novel approaches for vaccine development

Makda S Gebre  1 , Luis A Brito  2 , Lisa H Tostanoski  3 , Darin K Edwards  2 , Andrea Carfi  4 , Dan H Barouch  5
Affiliations
Review

Novel approaches for vaccine development

Makda S Gebre et al. Cell. .

Abstract

Vaccines are critical tools for maintaining global health. Traditional vaccine technologies have been used across a wide range of bacterial and viral pathogens, yet there are a number of examples where they have not been successful, such as for persistent infections, rapidly evolving pathogens with high sequence variability, complex viral antigens, and emerging pathogens. Novel technologies such as nucleic acid and viral vector vaccines offer the potential to revolutionize vaccine development as they are well-suited to address existing technology limitations. In this review, we discuss the current state of RNA vaccines, recombinant adenovirus vector-based vaccines, and advances from biomaterials and engineering that address these important public health challenges.

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Conflict of interest statement

Declaration of interests L.A.B., D.K.E., and A.C. are employees of Moderna Inc. and hold equities from the company. D.H.B. is a co-inventor on SARS-CoV-2 vaccine patents that have been licensed.

Figures

Figure 1:
Figure 1:
Process for mRNA vaccine development, from target identification to vaccination. (1) It starts with the identification and design of a target antigen, (2) Digital sequence design based on propriety algorithm, (3) Manufacturing of plasmid, mRNA, and lipid nanoparticle (LNP), (4) Fill, finish, and QC, (5) intramuscular injection, cellular uptake, protein expression, and immune activation
Figure 2:
Figure 2:
mRNA vaccines are composed of proprietary lipid nanoparticle delivery systems and mRNA optimized for stability and translation.
Figure 3:
Figure 3:
Process of adenovirus vector vaccine development. (1) First a vaccine antigen as well as an adenovirus vector with low seroprevalence are identified. (2) The gene sequence of the viral antigen is optimized and cloned into a shuttle plasmid. This plasmid is used to insert the antigen sequence into an adenoviral backbone in place of viral gene cassettes. (3) Then a primary viral stock is made in virus packaging cells and screened for antigen expression and function. (4) Lastly, the viral stock is amplified and purified for immunizations.
Figure 4:
Figure 4:
Characteristics of an adenoviral vaccine vector. Adenoviral vaccine vectors include a viral genome containing genes of antigen/s of interest for expression as well as viral capsid and fiber for cellular delivery.
Figure 5:
Figure 5:
Advantages of biomaterials in vaccine design. Encapsulation: allows for enhanced cellular uptake of vaccine antigen proteins, nucleic acids or small molecules as well as improved lymphoid organ drainage; Surface presentation: allows improved and regulated presentation of multiple copies of antigens for enhanced immune stimulation; Controlled release: allows for the regulation of the kinetics and availability of immunogens at different times post injection (LNP: lipid nanoparticle; NP: nanoparticle)
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