Table 2.
Summary of clinical trials for H5N1, H7N9, and H9N2 avian influenza vaccines.
| Subtype | Vaccine Description | Doses (Ag) | Phase | Outcomes | Trial ID | Reference |
|---|---|---|---|---|---|---|
| H5N1 | Inactivated whole virus adjuvanted (aluminum hydroxide) | 1.25, 2.5, 5, 10, 15, and 30 μg | 1, 2/3 | Safe and well-tolerated; two doses generated high levels of neutralizing antibodies |
NCT00356798 NCT02612909 |
94 96 |
| H7N9 | Inactivated whole virus adjuvanted (aluminum hydroxide) | 7.5, 15, and 30 μg | 1/2 | Safe and immunogenic; two doses induced an HI titer above 40 in 98.2% of participants | NCT03369808 | 97 |
| H9N2 | Inactivated whole virus nonadjuvanted | 3.75, 7.5, 15, 30, and 45 µg | 1/2 | Safe and well-tolerated; 52.8% to 88.9% of participants developed antibody levels predictive of protection | NCT01320696 | 98 |
| H5N1* | Split virus | 90 µg is approved. Tested: 7.5, 15, and 30 µg |
1/2, 3 | Safe and well-tolerated in all age groups; elicited neutralizing and HI titers; licensed in the US |
NCT00457509 NCT00415129 |
102 103 105 |
| H5N1* | Split virus adjuvanted (AS03) | 3.75 µg is approved. | 1/2, 3, 4 | Safe and well-tolerated; high neutralizing seroconversion rates; elicited robust antibody responses against homologous and heterologous strains; licensed in the US |
NCT00510874 NCT00616928 NCT01730378 NCT01788228 NCT01310413 |
107 108 109 |
| H5N1* | Subunit vaccine adjuvanted (MF59) | 7.5 µg is approved. Tested: 3.75 µg |
1/2, 3, 4 | Safe and well-tolerated; high seroconversion rates, elicited neutralizing antibodies and HI titers; licensed in the US |
NCT01776554 NCT02839330 NCT00812019 NCT01776541 |
111 112 113 114 |
| H7N9 | Subunit vaccine adjuvanted | 3.75, 7.5, and 15 µg | 1 | Safe; adjuvant was necessary to increase HI titers |
NCT01928472 NCT03682120 |
n/a |
| H9N2 | Subunit vaccine adjuvanted |
3.75, 7.5, 15, and 30 µg | 1 | Safe and well-tolerated; prime induced protective levels of antibodies | NCT00133471 | 99 |
| H7N9 | Split virus adjuvanted (oil-in-water IB160 or SE) | 3.75, 7.5, and 15 µg | 1 | Safe and well-tolerated; adjuvanted formulations elicited a significantly greater increase in antibody titers | NCT03330899 | 115 |
| H7N9 | Split virus adjuvanted (AS03) | 2.78, 3.75, and 5.08 µg | 1, 2 | Enhanced immune responses and good tolerability were observed compared to unadjuvanted or alum-adjuvanted formulations |
NCT01999842 NCT03318315 |
116 117 |
| H9N2 | Split virus adjuvanted (AS03) | 1.9, 3.75, and 15 µg | 1/2 | Safe and well-tolerated; the adjuvanted vaccine generated a seroconversion rate of ≥ 98.1%, both higher than the unadjuvanted vaccine | NCT01659086 | 118 |
| H5N1 | Live attenuated cold-adapted | 106.7 and 107.5 TCID50 | 1/2 | Safe, restricted in replication; IgA and IgG were detected by ELISA in the serum |
NCT00347672 NCT00488046 |
121 |
| H7N9 | Live attenuated cold-adapted | 107.5 TCID50 | 1 | Safe and well-tolerated; increase in neutralizing antibodies, serum IgG and IgA, mucosal IgA, CD4+, and CD8+ virus-specific T cells |
NCT02480101 NCT03739229 NCT01995695 NCT02274545 |
125 126 127 |
| H9N2 | Live attenuated cold-adapted | 107 and 2 × 107 TCID50 | 1 | Well-tolerated, exhibited an attenuated phenotype; Following two doses, 92% of participants showed greater than a 4-fold increase in HI titers, with 79% having a similar increase in neutralizing antibody titers | NCT00110279 | 128 |
| H5N1 | Virus-like particle | 5, 10, and 20 µg | 1, 2 | Well-tolerated; nearly 96% of individuals in the higher dose groups developed neutralizing antibody responses |
NCT00984945 NCT01991561 |
140 147 |
| H7N9 | Virus-like particle | 5, 15, and 30 µg | 1 | Well-tolerated; robust HI and neutralizing antibody responses | NCT01897701 | 141 |
| H7N9 | mRNA | 10, 25, and 50 µg | 1 | Safe and well-tolerated; 100% of participants seroconverted against the H7N9 strain. |
NCT03076385 NCT03345043 |
146 |
| H5N1 | Recombinant, protein-based adjuvanted (SE) Recombinant, protein-based adjuvanted (GLA/SE) |
3.8, 7.5 and 15 µg 3.8, 7.5, 15, 45, 135 µg |
1/2 1/2 |
Well-tolerated; 70% of participants receiving adjuvant seroconverted. Well-tolerated and immunogenic; GLA/SE improved serum antibody responses |
NCT01612000 NCT01147068 |
148 149 |
| H7N9 | Recombinant, protein-based adjuvanted (SE or MF59) | 7.5, 15, and 30 µg | 1/2 | Strong induction of anti-H7 antibodies; lacking neutralizing antibodies |
NCT02464163 NCT05608005 |
150 |
This table includes clinical trials, across all phases, with published results or results posted online. Trial IDs can be found at clinicaltrials.gov. * Vaccines that have been licensed for use in the United States by the United States Food and Drug Administration (FDA). Ag: antigen. AS03: adjuvant system 03; IB160: oil-in-water adjuvant emulsion; SE: stable emulsion; GLA/SE: glucopyranosyl lipid A/stable emulsion. n/a: a publication related to the clinical trial was not available.