Safety and Immunogenicity of an AS03-adjuvanted H5N1 Prepandemic Influenza Vaccine –A Phase III Study in Thai Population
Session VI – Prasert Auewarakul
Safety and Immunogenicity of an AS03-adjuvanted H5N1 Prepandemic Influenza Vaccine
–A Phase III Study in Thai Population
Prasert Thongcharoen1, Prasert Auewarakul1, Paul Gillard2, Hans L Bock2
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand1, GlaxoSmithKline Biologicals, Rixensart, Belgium2
Background: Manufacturing lead times result in late availability of a pandemic strain-specific vaccine for the victims of the first pandemic wave. Prepandemic influenza vaccination, administered before or just after the onset of a pandemic, is anticipated to mitigate the impact of the pandemic outbreak. GlaxoSmithKline’s AS03-adjuvanted prepandemic influenza vaccine containing 3.75 µg H5 haemagglutinin (HA) induced a strong immune response, had an acceptable reactogenicity and did not raise any safety concerns (Leroux-Roels et al, Lancet 370:580–9, 2007). As part of a larger Asian study, we assessed the immune response and safety of this vaccine formulation against clade 1 and clade 2.1 strains, in Thai adults.
Methods: This phase III study (109630/NCT00449670) involving 1,206 adults aged 18–60 years was conducted in 4 Asian sites, including Thailand (N=350). Subjects were vaccinated 21 days apart with two doses of H5N1 split virus prepandemic influenza vaccine containing 3.75 µg HA with or without AS03. At days 0, 21 and 42 (D42) serum samples were collected. Haemagglutination inhibition (HI) antibodies against the vaccine strain A/Vietnam/1194/2004 NIBRG-14 (clade 1) and also against A/Indonesia/05/2005 IBCDC-RG2 (clade 2.1) were measured and geometric mean titres (GMT), seroprotection rates (SPR) and seroconversion rates (SCR) were calculated. Solicited local and general symptoms, unsolicited adverse events and serious adverse events (SAEs) were recorded.
Results: D42 HI GMT, SPR and SCR against A/Vietnam/1194/2004 NIBRG-14 and A/Indonesia/05/2005 IBCDC-RG2 in the adjuvanted and non-adjuvanted groups of the Thai subjects in According-To-Protocol cohort for immunogenicity are shown in the table below:
|
THAI SUBJECTS |
AS03-Adjuvanted (n=277) |
Non-Adjuvanted (n=69) |
||
|
A/Vietnam/ 1194/2004 |
A/Indonesia/ 05/2005 |
A/Vietnam/ 1194/2004 |
A/Indonesia/ 05/2005 |
|
|
D42 GMT |
264.2 (229.6–304.1) |
34.2 (28.8–40.63) |
9.1 (7.2–11.5) |
5.6 (5.1–6.0) |
|
D42 SPR
|
94.9% (91.7–97.2) |
57.0% (51.0–62.9) |
18.8% (10.4–30.1) |
0% (0–5.2) |
|
D42 SCR |
94.2% (90.8–96.7) |
57.0% (51.0–62.9) |
4.3% (0.9–12.2) |
0% (0–5.2) |
Two doses of AS03-adjuvanted prepandemic influenza vaccine containing 3.75 µg H5 induced a marked immune response against the homologous and heterologous H5N1 strains. These immunogenicity data from the Thai population are consistent with those obtained from the entire Asian study population.
Although, the adjuvanted formulation elicited a higher incidence of local and general symptoms than the non-adjuvanted vaccine in the Thai population, the safety profile was acceptable. No SAEs related to vaccination were reported in the Thai population.
