Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in Humans and Agriculture

Abstract

Influenza virus infections pose a significant threat to public health due to annual seasonal epidemics and occasional pandemics. Influenza is also associated with significant economic losses in animal production. The most effective way to prevent influenza infections is through vaccination. Current vaccine programs rely heavily on the vaccine's ability to stimulate neutralizing antibody responses to the hemagglutinin (HA) protein. One of the biggest challenges to an effective vaccination program lies on the fact that influenza viruses are ever-changing, leading to antigenic drift that results in escape from earlier immune responses. Efforts toward overcoming these challenges aim at improving the strength and/or breadth of the immune response. Novel vaccine technologies, the so-called universal vaccines, focus on stimulating better cross-protection against many or all influenza strains. However, vaccine platforms or manufacturing technologies being tested to improve vaccine efficacy are heterogeneous between different species and/or either tailored for epidemic or pandemic influenza. Here, we discuss current vaccines to protect humans and animals against influenza, highlighting challenges faced to effective and uniform novel vaccination strategies and approaches.

Keywords: immune response; influenza vaccines; live attenuated vaccines; poultry; swine; universal vaccines; vaccine platform; vectored vaccine.

Figure 1

(Top) Schematic structure and genome organization of influenza A and B viruses. Haemagglutinin (HA), neuraminidase (NA), matrix protein 2 (M2/BM2), neuraminidase region B (NB) are on the surface of the virus particle. Matrix protein 1 (M1) is associated with the membrane. Ribonucleoprotein complex formed by RNA segments, nucleoprotein (NP) and viral polymerases (PB2, PB1, PA). Non-structural nuclear export protein (NEP). (Bottom) The 3D molecular structure of the HA glycoprotein trimer from A/Hong Kong/1/68 (H3N2) (PDB 5T6N), top (A) and side (B) views (structure modified and colored using MacPymol, Schrodinger, LLC). Each monomer has a globular head domain and a stem/stalk domain. On the left panels each monomer is shown with a different color. The receptor binding site (RBS) is highlighted in red. On the right panels, residue conservation for every position in the protein sequence is shown in a color scale, and visualized using the 3D tool available at the Influenza Research Database (www.fludb.org).

Figure 2

Immune response elicited by different influenza vaccines. (A) HA-head-specific antibodies interfere or block virus binding to the sialic acid receptors on the cell surface and prevent virus entry to host cells. (B) HA-stalk-specific antibodies prevent virus fusion to the endosome, inhibit budding and release of new virus particles, and mediate antibody dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells or complement activation. (C) NA-specific antibodies inhibit budding and release of new virus particles, and mediate ADCC by NK cells or complement activation. (D) M2e-specific antibodies inhibit budding and release of new virus particles, and mediate ADCC by NK cells, Fc-opsonization by macrophages or complement activation. (E) CD8+ T cells (cytotoxic T lymphocytes, or CTLs) recognize influenza peptides presented by major histocompatibility complex class I (MHC-I) at the surface of infected cells via their T cell receptor (TCR), release cytotoxic granules containing perforin and granzymes, resulting in lysis of infected cells.

Figure 3

Influenza “universal” vaccine platforms that are used in multiple species or epidemiological situations. Vaccine platform, types of technology, host species, type of immunity stimulated, breadth of protection, and types of universally protective vaccines within each platform are shown.