Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: GlaxoSmithKline Biologicals s.a., rue de lInstitut 89, B-1330 Rixensart, Belgium
Pharmacotherapeutic group: Influenza vaccines
ATC Code: J07BB02
This section describes the clinical experience with the pandemic preparedness vaccines.
Pandemic preparedness vaccines contain influenza antigens that are different from those in the currently circulating influenza viruses. These antigens can be considered as “novel” antigens and simulate a situation where the target population for vaccination is immunologically naïve. Data obtained with the pandemic preparedness vaccine will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical immunogenicity, safety and reactogenicity data obtained with pandemic preparedness vaccines are relevant for the pandemic vaccines.
In clinical studies that evaluated the immunogenicity of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 in subjects aged 18-60 years the anti-haemagglutinin (anti-HA) antibody responses were as follows:
| anti-HA antibody | Immune response to A/Vietnam/1194/2004 | ||||
| 0, 21 days schedule (D-Pan-H5N1-002) | 0, 6 months schedule (D-Pan-H5N1-012) | ||||
| 21 days after 1st dose N=925 | 21 days after 2nd dose N=924 | 21 days after 1st dose N=55 | 7 days after 2nd dose N=47 | 21 days after 2nd dose N=48 | |
| Seroprotection rate1 | 44.5% | 94.3% | 38.2% | 89.4% | 89.6% |
| Seroconversion rate2 | 42.5% | 93.7% | 38.2% | 89.4% | 89.6% |
| Seroconversion factor3 | 4.1 | 39.8 | 3.1 | 38.2 | 54.2 |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
3 seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-vaccination GMT.
After two doses given 21 days or 6 months apart, 96.0% of subjects had a 4-fold increase in serum neutralising antibody titres and 98-100% had a titre of at least 1:80.
Subjects of D-Pan-H5N1-002 were followed up for persistence of the immune response. The seroprotection rates 6, 12, 24 and 36 months after the first dose were as follows:
| anti-HA antibody | Immune response to A/Vietnam/1194/2004 | |||
| 6 months after the 1st dose N=256 | 12 months after the 1st dose N=559 | 24 months after the 1st dose N=411 | 36 months after the 1st dose N=387 | |
| Seroprotection rate1 | 40.2% | 23.4% | 16.3% | 16.3% |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40.
In a clinical study (Q-Pan-H5N1-001) in which two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/05/2005 were administered on days 0 and 21 to 140 subjects aged 18-60 years, the anti-HA antibody responses were as follows:
| anti-HA antibody | Immune response to A/Indonesia/05/2005 | ||
| Day 21 N=140 | Day 42 N=140 | Day 180 N=138 | |
| Seroprotection rate1 | 45.7% | 96.4% | 49.3% |
| Seroconversion rate2 | 45.7% | 96.4% | 48.6% |
| Seroconversion factor3 | 4.7 | 95.3 | 5.2 |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
3 seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-vaccination GMT.
A 4-fold increase in serum neutralising antibody titres was observed in 79.2% of subjects twenty-one days after the first dose, 95.8% twenty-one days after the second dose and 87.5% six months after the second dose.
In a second study, 49 subjects aged 18-60 years received two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/05/2005 on days 0 and 21. At day 42, the anti-HA antibody seroconversion rate was 98%, all subjects were seroprotected and the seroconversion factor was 88.6. In addition, all subjects had neutralising antibody titres of at least 1:80.
Anti-HA responses against A/Indonesia/5/2005 following administration of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 were as follows:
| anti-HA antibody | A/Indonesia/5/2005 | ||
| 0, 21 days schedule (D-Pan-H5N1-002) | 0, 6 months schedule (D-Pan-H5N1-012) | ||
| 21 days after 2nd dose N=924 | 7 days after 2nd dose N=47 | 21 days after 2nd dose N=48 | |
| Seroprotection rate*1 | 50.2% | 74.5% | 83.3% |
| Seroconversion rate2 | 50.2% | 74.5% | 83.3% |
| Seroconversion factor3 | 4.9 | 12.9 | 18.5 |
* anti-HA ≥1:40
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
3 seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-vaccination GMT.
A 4-fold increase in serum neutralising antibody against A/Indonesia/5/2005 was achieved in >90% of subjects after two doses regardless of the schedule. After two doses administered 6 months apart all subjects had a titre of at least 1:80.
Subjects from study D-Pan-H5N1-002 were followed up for persistence of anti-HA antibodies against A/Indonesia/5/2005. The seroprotection rates were 2.2%, 4.7%, 2.4% and 7.8% at months 6, 12, 24 and 36, respectively.
In a different study (D-Pan-H5N1-007) in 50 subjects aged 18-60 years the anti-HA antibody seroprotection rates 21 days after the second dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 were 20% against A/Indonesia/5/2005, 35% against A/Anhui/01/2005 and 60% against A/Turkey/Turkey/1/2005.
After two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/05/2005 administered on days 0 and 21 to 140 subjects aged 18-60 years, the anti-HA antibody responses to A/Vietnam/1194/2004 were as follows:
| anti-HA antibody | Immune response to A/Vietnam/1194/2004 | |
| Day 21 N=140 | Day 42 N=140 | |
| Seroprotection rate1 | 15% | 59.3% |
| Seroconversion rate2 | 12.1% | 56.4% |
| Seroconversion factor3 | 1.7 | 6.1 |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
3 seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-vaccination GMT.
At day 180, the seroprotection rate was 13%.
A 4-fold increase in serum neutralising antibody titres against A/Vietnam was obtained in 49% of subjects twenty-one days after the first dose, 67.3% twenty-one days after the second dose and 44.9% six months after the second dose.
An extended dosing interval was investigated in study D-H5N1-012 in which a group of subjects 18-60 years of age received two doses of Adjupanrix 6 months or 12 months apart. Twenty-one days after the second dose, the seroprotection rate and the vaccine response rate against A/Vietnam/1194/2004 in subjects who received the vaccine 6 months apart were 89.6% and 95.7%, respectively. Twenty-one days after the second dose, the seroprotection rate and the vaccine response rate in subjects who received the vaccine 12 months apart were 92.0% and 100%, respectively. In this study, cross-reactive immune responses against A/Indonesia/5/2005 were also observed.
Twenty-one days after the second dose, the seroprotection rate and the vaccine response rate in subjects who received the vaccine 6 months apart were 83.3% and 100%, respectively. Twenty-one days after the second dose, the seroprotection rate and the vaccine response rate in subjects who received the vaccine 12 months apart were 84.0% and 100%, respectively.
In a clinical study (D-Pan-H5N1-012), subjects aged 18-60 years received a dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from either A/Vietnam/1194/2004 or Indonesia/5/2005 six months after they had received one or two priming doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 on day 0 or on days 0 and 21 respectively. The anti-HA responses were as follows:
| anti-HA antibody | Against A/Vietnam 21 days after boosting with A/Vietnam N=46 | Against A/Indonesia 21 days after boosting with A/Indonesia N=49 | ||
| After one priming dose | After two priming doses | After one priming dose | After two priming doses | |
| Seroprotection rate1 | 89.6% | 91.3% | 98.1% | 93.9% |
| Booster seroconversion rate2 | 87.5% | 82.6% | 98.1% | 91.8% |
| Booster factor3 | 29.2 | 11.5 | 55.3 | 45.6 |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;
2 booster seroconversion rate: proportion of subjects who were either seronegative at pre-booster and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-booster and have a 4-fold increase in titre;
3 booster factor: ratio of the post-booster geometric mean titre (GMT) and the pre-booster GMT.
Regardless of whether one or two doses of priming vaccine had been given 6 months earlier, the seroprotection rates against A/Indonesia were >80% after a dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 and the seroprotection rates against A/Vietnam were >90% after a dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/05/2005. All subjects achieved a neutralising antibody titre of at least 1:80 against each of the two strains regardless of the HA type in the vaccine and the previous number of doses.
In another clinical study (D-Pan-H5N1-015), 39 subjects aged 18-60 years received a dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/5/2005 fourteen months after they had received two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 administered on day 0 and day 21. The seroprotection rate against A/Indonesia 21 days after booster vaccination was 92% and 69.2% at day 180.
In another clinical study (D-Pan-H5N1-038), 387 subjects aged 18-60 years received 1 dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Indonesia/5/2005 36 months after they had received two doses of A/Vietnam/1194/2004. The seroprotection rate, booster seroconversion rate and booster factor against A/Indonesia/5/2005 21 days after booster vaccination was 100%, 99.7% and 123.8, respectively.
In another clinical study (D-Pan-H5N1-010), 297 subjects aged >60 years (stratified in ranges from 61 to 70, 71 to 80 and > 80 years of age) received either a single or a double dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1) at 0 and 21 days. At day 42, the anti-HA antibody responses were as follows:
| anti-HA antibody | Immune response to A/Vietnam/1194/2004 (D42) | |||||
| 61 to 70 years | 71 to 80 years | >80 years | ||||
| Single dose N=91 | Double dose N=92 | Single dose N=48 | Double dose N=43 | Single dose N=13 | Double dose N=10 | |
| Seroprotection rate1 | 84.6% | 97.8% | 87.5% | 93.0% | 61.5% | 90.0% |
| Seroconversion rate2 | 74.7% | 90.2% | 77.1% | 93.0% | 38.5% | 50.0% |
| Seroconversion factor3 | 11.8 | 26.5 | 13.7 | 22.4 | 3.8 | 7.7 |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
3 seroconversion factor: ratio of the post-vaccination geometric mean titre (GMT) and the pre-vaccination GMT.
Although an adequate immune response was achieved at day 42 following two administrations of a single dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1), a higher response was observed following two administrations of a double dose of vaccine.
Very limited data in seronegative subjects >80 years of age (N=5) showed that no subject achieved seroprotection rate following two administrations of a single dose of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 (H5N1). However, following two administrations of a double dose of vaccine, the seroprotection rate at day 42 was 75%.
Subjects of D-Pan-H5N1-010 were followed up for persistence of the immune response. The seroprotection rates 6, 12 and 24 months after vaccination were as follows:
| anti-HA antibody | Immune response to A/Vietnam/1194/2004 | |||||
| 6 months after vaccination | 12 months after vaccination | 24 months after vaccination | ||||
| Single dose (N=140) | Double dose (N=131) | Single dose (N=86) | Double dose (N=81) | Single dose (N=86) | Double dose (N=81) | |
| Seroprotection rate1 | 52.9% | 69.5% | 45.3% | 44.4% | 37.2% | 30.9% |
1 seroprotection rate: proportion of subjects with haemagglutination inhibition (HI) titre ≥1:40.
In addition, 44.8% and 56.1% of subjects in respective dose groups had a 4-fold increase in serum neutralising antibody titres from day 0 to day 42 and 96.6% and 100% of subjects had a titre of at least 1:80 at day 42.
Twelve and twenty-four months after vaccination, the neutralising antibody titres were as follows:
| Serum neutralising antibody | Immune response to A/Vietnam/1194/2004 | |||
| 12 months after vaccination | 24 months after vaccination | |||
| Single dose N=51 | Double dose N=54 | Single dose N=49 | Double dose N=54 | |
| GMT1 | 274.8 | 272.0 | 391.0 | 382.8 |
| Seroconversion rate2 | 27.5% | 27.8% | 36.7% | 40.7% |
| ≥1:803 | 82.4% | 90.7% | 91.8% | 100% |
1 Geometric Mean Titre;
2 4-fold increase in serum neutralising antibody titre;
3 % of subjects reaching a serum neutralising antibody titre of at least 1:80.
In 297 subjects aged >60 years the anti-HA antibody seroprotection and seroconversion rates against A/Indonesia/5/2005 at day 42 after two doses of AS03-adjuvanted vaccine containing 3.75 µg HA derived from A/Vietnam/1194/2004 were 23% and the seroconversion factor was 2.7. Neutralising antibody titres of at least 1:40 or at least 1:80 were achieved in 87% and 67%, respectively, of the 87 subjects tested.
Subjects from study D-Pan-H5N1-010 who received a single dose were followed-up for persistence of anti-HA antibodies against A/Indonesia/5/2005. The seroprotection rates were 16.3% and 4.7% at months 12 and 24, respectively. Seroconversion rates for neutralising antibodies against A/Indonesia/5/2005 were 15.7% and 12.2% for months 12 and 24, respectively. The percentage of subjects reaching neutralising antibody titres of >1/80 were 54.9% and 44.9% at months 12 and 24, respectively.
In a clinical study (Q-Pan-H5N1-023), two doses of 0.125 ml containing the A/Indonesia/2005 H5N1 strain were administered on days 0 and 21 to 37 children aged 6 to <36 months.
Seroconversion rates for the anti-HA immune responses against homologous (A/Indonesia/05/2005) strain in this age group at Day 42 (21 days after the second dose) were as follows:
| anti-HA antibody | Immune response to A/Indonesia/05/2005 (0.125ml) |
| 21 days after 2nd dose (Day 42) N1=33 | |
| Seroconversion rate2 | 100% |
| Seroconversion factor3 | 168.2 |
1 according-to-protocol (ATP) immunogenicity cohort;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
3 seroconversion factor: ratio of the post-vaccination reciprocal HI titre to the pre-vaccination (Day 0) reciprocal HI titre.
In children 6 to <36 months of age who received a dose of 0.125 ml (Q-Pan H5N1-023), 100% (N=31) had a vaccine response rate for A/Indonesia/05/2005, 96.9% (N=32) had a vaccine response rate for heterologous strain A/Vietnam/1194/2004 and 96.9% (N=32) had a vaccine response rate for heterologous strain A/duck/Bangladesh/19097/2013.
Subjects enrolled in Q-Pan-H5N1-023 were followed up for persistence of the anti-HA immune response against the homologous A/Indonesia/05/2005 strain and heterologous A/duck/Bangladesh/19097, A/Vietnam/1194/2004 and A/gyrfalcon/Washington/41088-6/2014 strain after 12 months. The seroconversion rates 12 months after the second dose in children aged 6 to <36 months were as follows:
| anti-HA antibody | 0.125 ml | |||
| Immune response to A/Indonesia/05/2005 | Immune response to A/duck/Bangladesh/ 19097/2013 | Immune response to A/Vietnam/1194/2004 | Immune response to A/gyrfalcon/ Washington/4108 8-6/2014 | |
| 12 months after the 2nd dose N1=33 | 12 months after the 2nd dose N1=29 | 12 months after the 2nd dose N1=29 | 12 months after the 2nd dose N1=29 | |
| Seroconversion rate2 | 78.8% | 20.7% | 27.6% | 0% |
1 according-to-protocol (ATP) immunogenicity cohort at Day 385 (persistence);
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre.
For Q-PAN-H5N1-023 study, after primary vaccination with two doses of 0.125 ml containing A/Indonesia/2005 (H5N1) strain, one booster dose of same Q-H5N1 vaccine administered at Month 12. The anti-HA immune response against A/Indonesia/05/2005 was evaluated 7 days after the booster dose. The seroconversion rates are as follows:
| anti-HA antibody | 0.125 ml | |||
| Immune response to A/Indonesia/05/2005 | Immune response to A/duck/Bangladesh /19097/2013 | Immune response to A/Vietnam/1194/2004 | Immune response to A/gyrfalcon/Washington /41088-6/2014 | |
| 7 days after the booster dose N1=33 | 7 days after the booster dose N1=29 | 7 days after the booster dose N1=29 | 7 days after the booster dose N1=29 | |
| Seroconversion rate2 | 100% | 100% | 100% | 51.7% |
1 according-to-protocol (ATP) immunogenicity cohort at Day 392 post-booster dose;
2 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre.
In a clinical study (D-Pan-H5N1-032), two doses of 0.25 ml containing the A/Indonesia/2005 H5N1 strain were administered on days 0 and 21 to 312 children aged 3 to <18 years. The result below is presented from the group where subjects have received 2 doses (D0, D21) of H5N1 Indonesia and 1 booster dose (D182) of H5N1 Turkey (1.9µg HA + AS03B), 1 dose (D364) of Havrix. Twenty-one days after the second dose (Day 42), the immune responses in terms of seroconversion rate against the homologous strain were presented were as follows:
| anti-HA antibody | Immune response to A/Indonesia/05/2005 | Immune response to A/Turkey/01/2005 | ||
| 21 days after 2nd dose N1=155 | 21 days after 2nd dose N1=155 | |||
| 3 to <10 years N2=79 | 10 to <18 years N2=76 | 3 to <10 years N2=79 | 10 to <18 years N2=76 | |
| Seroconversion rate3 | 100% | 98.7% | 100% | 97.4% |
| Seroconversion factor4 | 118.9 | 78.3 | 36.2 | 21.0 |
1 Day 42 ATP cohort for immunogenicity cohort;
2 Day 42 ATP cohort for immunogenicity cohort for specific age category;
3 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
4 seroconversion factor: ratio of the post-vaccination reciprocal HI titre to the pre-vaccination (Day Day 0) reciprocal HI titre.
Subjects of D-Pan-H5N1-032 were followed up for persistence of the immune response against the homologous A/Indonesia/05/2005 strain and heterologous strain A/Turkey/01/2005 after 6 months. The seroconversion rates at Day 182 in children aged 3 to <18 years were as follows:
| anti-HA antibody | Immune response to A/Indonesia/05/2005 | Immune response to A/Turkey/01/2005 | ||
| 0, 21 days schedule | 0, 21 days schedule | |||
| Day 182 N1=155 | Day 182 N1=155 | |||
| 3 to <10 years N2=79 | 10 to <18 years N2=76 | 3 to <10 years N2=79 | 10 to <18 years N2=76 | |
| seroconversion rate3 | 83.5% | 73.7% | 55.7% | 40.8% |
| seroconversion factor4 | 10.2 | 8.1 | 6.2 | 5.1 |
1 Day 42 ATP cohort for immunogenicity cohort;
2 Day 42 ATP cohort for immunogenicity cohort for specific age category;
3 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
4 seroconversion factor: ratio of the post-vaccination reciprocal HI titre to the pre-vaccination (Day 0) reciprocal HI titre.
After primary vaccination with two doses of 0.25 ml containing A/Indonesia/2005 (H5N1) strain, one booster dose of D-H5N1 containing A/Turkey/2005/HA was administered at Month 6 to children aged 3 to <18 years (D-PAN-H5N1-032). Antibody immunogenicity at post-booster against A/Indonesia/05/2005 was evaluated at 10 days (Day 192) and persistence of antibody at 6 months (Day 364) after the booster dose. The seroconversion rates and seroconversion factors at these time points were as follows:
| anti-HA antibody | Immune response to A/Indonesia/05/20051 | ||
| Day 192 N1=127 | |||
| 3 to <10 years N2=68 | 10 to <18 years N2=59 | ||
| seroconversion rate5 | 100% | 100% | |
| seroconversion factor6 | 142.6 | 94.4 | |
| Day 364 N3=151 | |||
| 3 to <10 years N4=79 | 10 to <18 years N4=72 | ||
| seroconversion rate5 | 100% | 100% | |
| seroconversion factor6 | 42.4 | 30.4 | |
1 Month 6 ATP cohort for immunogenicity;
2 Month 6 ATP cohort for immunogenicity for specific age category;
3 Month 12 ATP cohort for immunogenicity;
4 Month 12 ATP cohort for immunogenicity for specific age category;
5 seroconversion rate: proportion of subjects who were either seronegative at pre-vaccination and have a protective post-vaccination titre of ≥1:40, or who were seropositive at pre-vaccination and have a 4-fold increase in titre;
6 seroconversion factor: ratio of the post-vaccination reciprocal HI titre to the pre-vaccination (Day 0) reciprocal HI titre.
Similar immunogenicity results for the primary vaccination were obtained in a clinical study (D-PANH5N1-009) conducted in 102 children 3 to 5 and 6 to 9 years of age who received 2 doses of 0.25 ml of Adjupanrix containing A/Vietnam/1194/2004. Furthermore, this study evaluated persistence against homologous A/Vietnam/1194/2004 up to 24 months after the second dose. The seroconversion rate was 38.3% for 3-5 year olds and 22.9% for 6-9 year olds at Month 24. Cross-reactive antibody responses against the heterologous strain A/Indonesia/05/2005 were also observed and, although declining persisted up to 24 months after the second dose.
Information from non-clinical studies:
The ability to induce protection against homologous and heterologous vaccine strains was assessed non-clinically using ferret challenge models.
In each experiment, four groups of six ferrets were immunised intramuscularly with an AS03 adjuvanted vaccine containing HA derived from H5N1/A/Vietnam/1194/04 (NIBRG-14). Doses of 15, 5, 1.7 or 0.6 micrograms of HA were tested in the homologous challenge experiment, and doses of 15, 7.5, 3.8 or 1.75 micrograms of HA were tested in the heterologous challenge experiment. Control groups included ferrets immunized with adjuvant alone, non-adjuvanted vaccine (15 micrograms HA) or phosphate buffered saline solution. Ferrets were vaccinated on days 0 and 21 and challenged by the intra-tracheal route on day 49 with a lethal dose of either H5N1/A/Vietnam/1194/04 or heterologous H5N1/A/Indonesia/5/05. Of the animals receiving adjuvanted vaccine, 87% and 96% were protected against the lethal homologous or heterologous challenge, respectively. Viral shedding into the upper respiratory tract was also reduced in vaccinated animals relative to controls, suggesting a reduced risk of viral transmission. In the unadjuvanted control group, as well as in the adjuvant control group, all animals died or had to be euthanized as they were moribund, three to four days after the start of challenge.
This medicinal product has been authorised under ‘exceptional circumstances’.
This means that for scientific reasons it has not been possible to obtain complete information on this medicinal product.
The European Medicines Agency will review any new information which may become available every year and this SmPC will be updated as necessary.
Not applicable.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, acute and repeated dose toxicity, local tolerance, female fertility, embryo-foetal and postnatal toxicity (up to the end of the lactation period).
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