Novel Platforms for the Development of a Universal Influenza Vaccine

Abstract

Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines. This review discusses recent scientific advances in the development of next-generation universal influenza vaccines.

Keywords: functional antibody responses; hemagglutinin; influenza; neutralizing antibodies; universal flu vaccine; vaccination strategies; virus-like particles.

Figure 1

Approaches for universal influenza vaccine development. (A) VLP platform: VLPs produced by cloning of HA, NA, and M1 gene sequences of influenza virus into the expression vector followed by transfection in to insect cells. Co-expression of HA, NA, and M1 proteins allows self-assembly of VLPs. (B) Synthetic-virus platform: MDCK cells are transfected with plasmid DNA encoding influenza-virus backbone genes and error-free HA and NA gene segments, synthesized by an enzymatic and cell-free assembly technique. After transfection, vaccine viruses are rescued from MDCK cells. (C) DNA-vaccine platform: influenza genes encoding antigenic proteins are inserted into a DNA plasmid and delivered to the host cells, where DNA vaccines express antigenic protein. (D) RNA-vaccine platform: self-amplifying RNA expressed from an alphavirus genome in which structural genes are replaced by genes supporting the amplification of the RNA and the gene encoding the antigen. Self-amplifying mRNA (SAM) composed of a 5′ cap, genes encoding non-structural genes (NSP 1–4), a subgenomic promoter, the antigen-encoding gene, and a 3′ poly(A) tail. Diagrammatic representation of a lipid nanoparticle (LNP) encapsulating SAM. (E) Viral-vector platform: viral vector-based influenza vaccine uses a non-influenza “carrier” virus to express antigenic protein. Influenza genes encoding HA protein are placed in to the carrier virus vector to express HA protein on the virus surface. Abbreviations: HA, hemagglutinin; NA, neuraminidase; M1, matrix protein 1; VLP, virus-like particle; MDCK, Madin–Darby kidney cells.