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Review
. 2012 Aug;11(8):995-1007.
doi: 10.1586/erv.12.70.

Virus-like particles as universal influenza vaccines

Sang-Moo Kang  1 , Min-Chul Kim, Richard W Compans
Affiliations
Review

Virus-like particles as universal influenza vaccines

Sang-Moo Kang et al. Expert Rev Vaccines. 2012 Aug.

Abstract

Current influenza vaccines are primarily targeted to induce immunity to the influenza virus strain-specific hemagglutinin antigen and are not effective in controlling outbreaks of new pandemic viruses. An approach for developing universal vaccines is to present highly conserved antigenic epitopes in an immunogenic conformation such as virus-like particles (VLPs) together with an adjuvant to enhance the vaccine immunogenicity. In this review, the authors focus on conserved antigenic targets and molecular adjuvants that were presented in VLPs. Conserved antigenic targets that include the hemagglutinin stalk domain, the external domain of influenza M2 and neuraminidase are discussed in addition to molecular adjuvants that are engineered to be incorporated into VLPs in a membrane-anchored form.

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Figures

Figure 1
Figure 1. Schematic diagrams of influenza virions and virus-like particles
(A) Influenza virion showing surface proteins, HA, NA, ion channel protein M2 and viral nucleoproteins. (B) HA VLPs: influenza VLPs containing matrix protein M1 and HA. (C) NA VLPs: influenza VLPs containing matrix protein M1 and NA. (D) Chimeric HA VLPs: influenza VLPs containing matrix protein M1, HA and a molecular adjuvant such as GM-CSF, CD40 ligand or flagellin as immune-stimulating molecules. (E) M2 VLPs: influenza VLPs containing matrix proteins M1 and M2. The matrix protein (M1) is thought to be positioned along the inner surface of the membrane and stabilizes the particle [147]. HA: Hemagglutinin; NA: Neuraminidase; VLP: Virus-like particle.
Figure 2
Figure 2. HA2 stalk domain and virus-like particles
(A) HA1–HA2 subunits: the HA1 subunit contains the globular head domain (HA1 head), a major antigenic target of current vaccination. The HA2 subunit contains the FP, the LAH domain and TM-CT. The FP domain includes 11 highly conserved amino acids in the N-terminal cleavage region and the presumed fusion peptide region of amino acids 1–38. The LAH region contains the amino acids 76–130, a region recognized by monoclonal antibody 12D1 [28]. (B) A diagram of a headless HA protein design reported by Steel et al. [42]. A SP and HA1 subunit C-terminal adjoining region (HA1c) with the globular head domain deleted are connected to the HA1 subunit for expression on the cell surfaces [42]. (C) A schematic diagram of headless HA-containing VLPs. FP: Fusion peptide; HA: Hemagglutinin; LAH: Long α-helix; SP: Signal peptide; TM-CT: Transmembrane-cytoplasmic tail; VLP: Virus-like particle.
Figure 3
Figure 3. A model of influenza viral surface proteins and virus-like particles expressing influenza surface proteins separately
(A) The viral surface is represented with large trimeric globular HA, tetrameric NA and small tetrameric M2. (B) Influenza VLP surface expressing influenza HA, NA or M2 protein. HA: Hemagglutinin; NA: Neuraminidase; VLP: Virus-like particle.
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