Table 1.
Select broadly protective vaccine candidates targeting the conserved regions of Influenza viruses.
| Vaccine target |
Vaccine approach [antigen] |
Test species |
Immune response mediating protection |
Protection conferred against influenza viruses |
Challenge influenza virus dose |
References | |
|---|---|---|---|---|---|---|---|
| 1 | HA stem | Peptide vaccine [LAH portion of A/HK/1/68(H3N2)] | Mice | Antibodies to HA stem | PR8/H1N1 A/VN/1203/04 (H5N1) A/HK/1/68-PR8 (H3N2) | 10–15 MLD50 | [30] |
| 2 | HA fusion peptide | Peptide vaccine [Fusion peptide of A/Mississippi/1/85 (H3N2)] | Mice | Antibodies to HA fusion peptide | PR8/H1N1 A/Mississippi/1/85 (H3N2) | 1 MLD50 | [39] |
| 3 | M2 | Recombinant protein [M2 of A/Ann Arbor/6/60 (H2N2)] | Mice | Antibodies to M2 | A/Ann Arbor/6/60 (H2N2) A/HK/1/68 (H3N2) | 10 MLD50 | [46] |
| 4 | M2 | Recombinant protein [M2 of A/ Aichi/ 2/68 (H3N2)] | Mice | Antibodies to M2 | A/Ann Arbor/6/60 (H2N2) A/Taiwan/1/86 (H1N1) A/HK/1/68 (H3N2) | 1×105 – 5 ×106 EID50 | [47] |
| 5 | M2 | DNA/Ad [M2 protein of PR8/H1N1] | Mice | Antibodies to M2 | PR8/H1N1 A/Thailand/Sp-83/04 (H5N1) | 1.5×104 MLD50 of PR8/H1N1 virus, and 10 MLD50 of A/Thailand/Sp-83/04 (H5N1) | [50] |
| 6 | M2, HA | DNA [M2 and HA of H1N1 virus] | Mice | Antibodies to HA and M2 | A/Korea/W81/05 (H3N2) | 5 MLD50 | [52] |
| 7 | M2, NP | Ad [M2 of H1N1, H5N1, and H7N2 and NP of H1N1] | Mice | Antibodies to M2 and CMI to NP | PR8/H1N1 A/Fort Monmouth/1/47 (H1N1) | 10–150 MLD50 of PR8/H1N1, and 3–10 LD50 of A/Fort Monmouth/1/47 (H1N1) | [51] |
| 8 | M2e, NP | Recombinant protein [M2e and NP epitopes fused to HBc] | Mice | Antibodies to M2 and CMI to NP | A/Beijing/501/2009 (H1N1) A/ostrich/Suzhou/097/2003 (H5N1) | 50 LD50 of A/Beijing/501/2009 (H1N1), and 10 LD50 of A/ostrich/ Suzhou/097/2003 (H5N1) | [48] |
| 9 | NP | Recombinant protein [NP of X31 (H3N2) virus] | Mice | CMI to NP | PR8/H1N1 | 8–16 LD50 | [59] |
| 10 | HA, NP, and M1 | DNA [HA of A/Hawaii/01/91 (H3N2) and NP & M1 of A/Beijing/353189 (H3N2)] | Ferrets | Antibodies to HA, and CMI to NP and M1 | A/Georgia/03193 (H3N2) A/Johannesburg/33194 (H3N2) | 200 × 50% ferret infectious dose | [61] |
| 11 | NP, M1 | DNA [NP and M1 of PR8/H1N1] | Mice | CMI to NP and M1 | A/Hong Kong/483/97 (H5N1) A/Hong Kong/156/97 (H5N1) | 100–10,000 MID50 | [63] |
| 12 | NP | DNA-Ad [NP of PR8/H1N1] | Mice | CMI to NP | PR8/H1N1 A/Hong Kong/483/97 (H5N1) A/Hong Kong/156/97 (H5N1) | 10–10,000 MID50 | [32] |
| 13 | NP | Ad [NP of PR8/H1N1] | Mice | CMI to NP | PR8/H1N1 A/Philippines/2/82 (H3N2) A/VN/1203/04 (H5N1) | 10 MLD50 | [62] |
| 14 | NP | Ad [NP of PR8/H1N1] | Mice | CMI to NP | PR8/H1N1 A/VN/1203/04 (H5N1) A/Hong Kong/ 483/1997 (H5N1) | 100 MLD50 | [67] |
| 15 | NP, M2 | Ad [Consensus NP and M2 genes] | Mice | CMI to NP and antibodies to M2 | A/Fort Monmouth/1/47-ma (H1N1) | 104 TCID50 | [122] |
| 16 | HA, NP | MVA [HA of A/California/04/09 (H1N1) virus, and NP of A/VN/1203/04 (H5N1)] | Mice | Antibodies to HA. and CMI to NP | A/VN/1203/04 (H5N1) A/Norway/3487-2/09 (H1N1) PR8/H1N1 A/Aichi/68 (H3N2) | 100 MLD50 | [64,69] |
| 17 | NP | PIV5 [NP from A/VN/1203/04 (H5N1)] | Mice | CMI to NP | A/VN/1203/04 (H5N1) PR8/H1N1 | 10 MLD50 | [75,76] |
Abbreviations: HA, hemagglutinin; M2, M2 ion channel protein; M2e, ectodomain of M2 protein; M1, M1 matrix protein; NP, nucleoprotein; LAH, long alpha helix; CMI, cell-mediated immunity; MLD50, 50% mouse lethal dose; MID50, 50% mouse infectious dose; EID50, 50% egg infectious dose; Ad, adenoviral vector; MVA, Modified vaccinia Ankara virus; HBc, hepatitis B core antigen; PR8/H1N1, A/Puerto Rico/8/1934 (H1N1); A/VN/1203/04 (H5N1), A/Vietnam/1203/2004 (H5N1); A/HK/1/1968 (H3N2), A/Hong Kong/1/1968 (H3N2); X-31, A/Hong Kong/1/68-PR8 (H3N2); A/X-47 (H3N2), A/Victoria/3/75(H3N2)×PR8.