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Initiative for Vaccine Research (IVR)
  WHO > Programmes and projects > Initiative for Vaccine Research (IVR) > Selection of Diseases in IVR Portfolio
printable version

Tables on the Clinical trials of pandemic influenza prototype vaccines: Previous page | 1,2,3,4

Complete data set

Basic Information | Basic + immunogenicity results | Complete data set

Type of vaccine Producer Subtype Strain Substrate Adjuvant Dose µg Clinical phase Number of subjects Age Schedule Route of admin. Immunogenicity (trial-to-trial comparison cannot be done as study design and tests are not standardized) Timing Reference Comments
Per cent responders at specified titer Seroconversion rate GMT increase
Inactivated whole virion Baxter (Czech Republic/ Austria) H5N1 Wild type strain: A/Vietnam/1203/2004 Vero cells None, Al(OH)3 3.75, 7.5, 15, 30, 45 I/II 270 18-45 Two doses on days 0, 21 IM NT≥20 (after two doses)
66% (30µg+Alum)
61% (15µg+Alum)
64% (7.5µg+Alum)
69% (3.75µg+Alum)
71% (15µg no Alum
76% (7.5µg no Alum) 		Results not publicly available Fold increase in NT (after 2 doses) =
4.6 (30µg+Alum)
3.9 (15µg+Alum)
4.0 (7.5µg+Alum)
4.4 (3.75µg+Alum)
5.7 (15µg no Alum)
5.3 (7.5µg no Alum)		 Start 2006 *** (O. Kistner) The vaccine shows cross-neutralization against an old prototype strain (Hongkong/156/1997) as well as against a recent clade 2 strain (Indonesia/05/2005)
Inactivated whole virion Berna Biotech, Switzerland - Solvay, Netherlands H9N2 A/Hong Kong/1073/99 Eggs none 7.5, 15, 30 I 30 18-60 Two doses on days 0, 21 IM HI≥40 (after 2 doses)=
43% (in subjects aged≤ 32 yrs)
66% (in subjects aged≥32yrs)		 HI≥4 fold increase (after two doses) =
64% (in subjects aged≤ 32 yrs)
75% (in subjects aged≥ 32yrs)		 Fold increase in HI (after 2 doses) =
6.9 (in subjects aged< 32 yrs)
3.0 (in subjects aged≥ 32 yrs)		 2000 Lancet, 2003, 362, 1959-1967 In immunologically naive subjects whole virion vaccine was more immunogenic than subunit vaccine.
Inactivated whole virion Berna Biotech - Crucell, Switzerland H9N2 A/Hong Kong/1073/99 Egg Al(OH)3
None
Virosomes		 1.7, 5, 15, 45 5, 15 1.7, 5, 15, 45 II 560 >18 Two doses IM ID No data No data No data 2006-2007 No data With participation of Leicester Royal Infirmary
Inactivated whole virion Biken, Japan H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 1.7, 5, 15 I/II 120 20-40 Two doses on days 0, 21 IM SC & NT≥40 (after 2 doses) =
IM SC
84% 71% (15µg+Alum)
61% 61% (5µg+Alum)
41% 34% (1.7µg+Alum)
& NT≥4 fold increase (after 2 doses) =
IM SC
96% 84% (15µg+Alum)
71% 72% (5µg+Alum)
43% 50% (1.7µg+Alum)
No data 2006 Abstract *** (M. Tashiro)
Inactivated whole virion Denka Seiken, Japan H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 1.7, 5, 15 I/II 120 20-40 Two doses on days 0, 21 IM SC
& NT≥40 (after 2 doses) =
IM SC
84% 71% (15µg+Alum)
61% 61% (5µg+Alum)
41% 34% (1.7µg+Alum)

& NT≥4 fold increase (after 2 doses) =
IM SC
96% 84% (15µg+Alum)
71% 72% (5µg+Alum)
43% 50% (1.7µg+Alum)
No data 2006 Abstract *** (M. Tashiro)  
Inactivated whole virion Kitasato Institute, Japan H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 1.7, 5, 15 I/II 120 20-40 Two doses on days 0, 21 IM, SC
& NT≥40 (after 2 doses) =
IM SC
84% 71% (15µg+Alum)
61% 61% (5µg+Alum)
41% 34% (1.7µg+Alum)

& NT≥4 fold increase (after 2 doses)=
IM SC
96% 84% (15µg+Alum)
71% 72% (5µg+Alum)
43% 50% (1.7µg+Alum)
No data 2006 Abstract *** (M. Tashiro)
Inactivated whole virion Kaketsuken, Japan H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 1,7, 5, 15 I/II 120 20-40 Two doses on days 0, 21 SC No data No data No data Start 2006 Abstract *** (M. Tashiro)
Inactivated whole virion GSK Biologicals, Belgium H2N2 A/Singapore/1/57 Egg AlPO4 Al(OH)3 1.9, 3.8, 7.5, 15 I/II 196 18-30 unprimed
Two doses on days 0, 21 		IM HI≥40 =
98%(15µg non Alum, split)
87% (7.5µg+Alum)
98% (3.8µg+Alum)
82% (1.9µg+Alum) 		HI≥4 fold increase =
98% (15µg non Alum, split)
87% (7.5µg+Alum)
98% (3.8µg+Alum)
80% (1.9µg+Alum) 		HI fold increase =
23.4 (15µg non Alum, split)
14.8 (7.5µg+Alum)
17.2 (3.8µg+Alum)
11.3 (1.9µg+Alum) 		2000 (completed) Med Microbiol Immunol, 2002, 191, 203-208

Virus Res 2004, 103 (1-2),163-171 * (N. Hehme)
Inactivated whole virion GSK Biologicals, Belgium H2N2 A/Singapore/1/57 Egg AlPO4 Al(OH)3 1.9, 3.8, 7.5, 15 I/II 149 31-60 primed Two doses on days 0, 21 IM Results not publicly available Results not publicly available Results not publicly available 2000 (completed) No data
Inactivated whole virion GSK Biologicals, Belgium H2N2 A/Singapore/1/57 Egg AlPO4 Al(OH)3 1.9, 3.8, 7.5, 15 I/II 45 >60 primed Two doses on days 0, 21 IM Results not publicly available Results not publicly available Results not publicly available 2000 (completed) No data
Inactivated whole virion GSK Biologicals, Belgium H2N2 A/Singapore/1/57 Egg AlPO4 Al(OH)3 1.9, 15 I/II 38 18-30 Two doses on days 0, 21 IM Results not publicly available Results not publicly available Results not publicly available 2001 (completed) No data
Inactivated whole virion GSK Biologicals, Belgium H2N2 A/Hong Kong/1073/99 Egg AlPO4 Al(OH)3 1.9, 3.8, 7.5, 15 I//II 194 18-30 Two doses on days 0, 21 IM HI≥40 (after 2 doses) =
67% (15µg no Alum)
82% (7.5µg+Alum)
68% (3.8µg+Alum)
71% (1.9µg+Alum) 		HI≥4 fold increase(after 2 doses) =
65% (7.5µg+Alum)
72% (3.8µg+Alum)
54% (1.9µg+Alum)
58% (15µg no Alum) 		Fold increase in HI (after 2 doses) =
8.4 (15µg no Alum)
9.3 (7.5µg+Alum)
5.9 (3.8µg+Alum)
6.1 (1.9µg+Alum) 		2001 (completed) Med Microbiol Immunol, 2002, 191 (3-4), 203-208
Inactivated whole virion GSK Biologicals, Belgium H9N2 A/Hong Kong/1073/99 Egg AlPO4 Al(OH)3 1.9, 3.8, 7.5, 15 I/II 385 >60 Two doses on days 0, 21 IM HI≥40 (after 2 doses) =
52% (7.5µg+Alum)
41% (3.8µg+Alum)
31% (1.9µg+Alum)
56% (15µg non Alum)
41% (7.5µg no Alum)
41% (3.8µg non Alum)
20% (1.9µg non Alum) 		HI≥4 fold increase(after 2 doses) =
65% (7.5µg+Alum)
46% (3.8µg+Alum)
37% (1.9µg+Alum)
75% (15µg no Alum)
51% (7.5µg non Alum)
51% (3.8µg non Alum)
26% (1.9µg non Alum) 		Fold increase in HI (after 2 doses) =
8.3 (7.5µg+Alum)
4.9 (3.8µg+Alum)
3.7 (1.9µg+Alum)
6.3 (15µg non Alum)
4.9 (7.5µg non Alum)
4.3 (3.8µg non Alum)
2.9 (1.9µg non Alum) 		2005 Med Microbiol Immunol, 2002, 191 (3-4), 203-208

Internat. Conf. on Influenza Vaccines for the World – IVW, Vienna 18-20 October 2006 *** (N. Hehme)
Inactivated whole virion GSK Biologicals, Belgium H5N1 A/Vietnam/1194/2004 Egg AlPO4 Al(OH)3 3.8, 7.5, 15, 27 II 400 18-60 Two doses on days 0, 21 IM HI≥40 (after 2 doses) =
90% (27mg+Alum)
71% (15mg+Alum)
63% (7.5mg+Alum)
69%(3.8mg+Alum)
71% (27mg non Alum)
70% (15mg non Alum)
58% (7.5mg non Alum)
51%(3.8mg non Alum) 		HI≥4 fold increase (after 2 doses) =
90% (27mg+Alum)
71% (15mg+Alum)
63% (7.5mg+Alum)
67% (3.8mg+Alum)
71% (27mg non Alum)
0% (15mg non Alum)
58% (7.5mg non Alum)
51% (3.8mg+ non Alum) 		Fold increase in HI (after 2 doses) =
32.4 (27mg+Alum)
12.4 (15mg+Alum)
9.1 (7.5mg+Alum)
10.5 (3.8mg+Alum)
13.0 (27mg non Alum)
10.9 (15mg non Alum)
7.9 (7.5mg non Alum)
5.7 (3.8mg non Alum) 		2006 Internat. Conf. on Influenza Vaccines for the World – IVW, Vienna 18-20 October 2006 *** (N. Hehme) EMEA: Centrally authorised pandemic influenza 'mock-up' vaccines on 21 March 2007 Trade mark: Daronix
Inactivated whole virion Nobilon International BV, Netherlands H5N1 A/Vietnam/1194/2004 Cell Al(OH)3 3.8, 7.5, 15, 30 I/II 425 18-60 >60 Two doses IM No data No data No data Start 2007

Inactivated whole virion Omninvest Hungary H5N1 A/Vietnam/1194/2004 Egg AlPO4 6
146 18-73 Single dose IM HI≥40 = 63.7% HI≥4 fold increase = 63.7% HI fold increase in HI = 5.6 2005-2006 (completed) Emerg. Infect. Dis (CDC), 2007, 13, 5
Inactivated whole virion Omninvest Hungary H5N1 A/Vietnam/1194/2004 Egg AlPO4 6
12 3-18 Single dose IM No data No data No data Start 2006 Abstract
Inactivated whole virion Omninvest Hungary H5N1 A/Vietnam/1194/2004 Egg AlPO4 3.5, 6, 12
480 18-60 <60 Single dose with option of second dose IM No data No data No data Start 2006 Abstract
Inactivated whole virion Sinovac Biotech, China H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 1.25, 2.5, 5, 10 I 120 18-60 Two doses, days 1, 28 IM HI≥40 (after 2 doses)=
78%(10µg+Alum)
33% (5µg+Alum)
29% (2.5µg+Alum)
13% (1.25µg+Alum) 		HI≥4 fold increse (after 2 doses) =
78%(10µg+Alum)
33% (5µg+Alum)
21% (2.5µg+Alum)
13% (1.25µg+Alum) 		Fold increase in HI (after two doses) =
11.5 (10µg+Alum)
4.9 (5µg+Alum)
2.7 (2.5µg+Alum)
2.7 (1.25µg+alum) 		2005-2006 Lancet, 2006, 368, 9540, 991-997 *** (Lin Su) Further trials with 5, 10 and 15µg are planned
Inactivated split virus CSL Ltd, Australia H5N1 A/Vietnam/1194/2004 Egg AlPO4 7.5, 15 I/II 198 18-45 Two doses on days 0, 21 followed by a 6 month booster dose IM After two doses:
HI≥40 =
37% (15µg+Alum)
34% (7.5µg+Alum)
NT≥40 =
41% (15µg+ Alum)
34% (7.5µg+ Alum) 		After two doses
HI≥4 fold increase =
35% (15µg+Alum)
34% (7.5µg+Alum)
NT≥40 =
41% (15µg+ Alum)
34% (7.5µg+ Alum) 		After two doses
fold increase in HI =
4.5 (15µg+Alum)
4.9 (7.5µg+Alum)
in NT =
2.8 (15µg+ Alum)
2.1 (7.5µg+ Alum) 		2005-2007 ***(T. Nolan) Clinical trials of H5N1 vaccine with ISCOMATRIX (saponin-based adjuvant) are planned for 2007
Inactivated split virus CSL Ltd, Australia H5N1 A/Vietnam/1194/2004 Egg AlPO4 30, 45 I/II 392 18-64 Two doses on days 0, 21 IM After two doses:
HI≥40 =
50% (15µg+Alum)
50% (7.5µg+Alum)
in NT≥40 =
55% (15µg+ Alum)
54% (7.5µg+ Alum)		 After two doses:
HI≥4 fold increase =
49% (15µg+Alum)
48% (7.5µg+Alum)
in NT≥4 fold increase =
55% (15µg+ Alum)
54% (7.5µg+ Alum)		 After two doses:
fold increase in HI =
7.3 (15µg+Alum)
6.8 (7.5µg+Alum)
in NT =
4.5 (15µg+ Alum)
4.3 (7.5µg+ Alum) 		2006-2007 ***(T. Nolan) Clinical trials of H5N1 vaccine with ISCOMATRIX (saponin-based adjuvant) planned for 2007
Inactivated split virus CSL Ltd, Australia H5N1 A/Vietnam/1194/2004 Egg AlPO4 30, 45 II 220 Child:6 m - 8 years Two doses IM No data No data No data 2006-2007 No data
Inactivated split virus CSL Ltd, Australia H5N1 A/Vietnam/1194/2004 Egg AlPO4 30, 45 II 200 >65 Two doses IM No data No data No data 2006-2007 No data  
Inactivated split virus GSK Biologicals, Belgium H5N1 A/Vietnam/1194/2004 Egg AS 3.8, 7.5, 15, 30 I/II 400 18-60 Two doses on days 0, 21 IM HI≥40(after 2 doses) =
85% (30µg+AS)
96% (15µg+AS)
90% (7.5µg+AS)
84% (3.8µg+AS)
43% (30µg non-adjuvanted) 35% (15µg non-adjuvanted) 16% (7.5µg non-adjuvanted)
4% (3.8µg non-adjuvanted) 		HI≥4 fold increase (after 2 doses) =
85% (30µg+AS)
96% (15µg+AS)
90% (7.5µg+AS)
84% (3.8µg+AS)
41% (30µg non-adjuvanted)
35% (15µg non-adjuvanted)
16% (7.5µg non-adjuvanted)
4% (3.8µg non-adjuvanted) 		Fold increase in HI (after 2 doses) = 36.4 (30µg+AS)
60.5 (15µg+AS)
38.1 (7.5µg+AS)
27.9 (3.8µg+AS)
3.9 (30µg non-adjuvanted)
2.8 (15µg non-adjuvanted)
1.7 (7.5µg non-adjuvanted)
1.2 (3.8µg non-adjuvanted) 		2006 Internat. Conf. on Influenza Vaccines for the World – IVW, Vienna 18-20 October 2006
***(N. Hehme) 		Cross-reactivity against Clade 2 virus was shown in sera of vaccinees. Mock-up file submitted to EMEA in Dec 2006
Inactivated split virus Sanofi Pasteur, France H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 7.5, 15, 30 I 300 18-40 Two doses on days 1, 21 IM HI≥32 (after 2 doses) =
67% (30µg+Alum)
44% (15µg+Alum)
52% (30µg no Alum)
44% (15µg no Alum)		 HI≥4 fold increase (after 2 doses) =
66% (30µg+Alum)
44% (15µg+Alum)
53% (30µg no Alum)
44%(15µg+Alum) 		Fold increase in HI (after 2 doses) = 11.6 (30µg+Alum)
4.3 (15µg+Alum)
6.8% (30µg no Alum)
4.5 (15µg no Alum)		 2005 Lancet, 2006 367, 1657-1664
**(C. Gerdil-Lacroix ) 		Results in HI and NT were comparable
Inactivated split virus Sanofi Pasteur, France H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 7.5, 30 II 600 >60 Two doses on days 1, 21 IM Results not publicly available Results not publicly available Results not publicly available 2006 *** (A. Hoffenbach) Cross-neutlizatiom with Clade 2 virus was shown in sera of vaccinees
Inactivated split virus Sanofi Pasteur, France H7N1 A/chicken/Italy H7N1xPR8(RD-3) PER.C6 cells Al(OH)3 12, 24 I 60 20-40 Two doses on days 1, 21 IM No data No data No data Start 2006 No data FLUPAN consortium
Inactivated split virus Sanofi Pasteur, USA H5N1 A/Vietnam/1203/2004 Egg None 7.5, 15, 45, 90 I/II 451 18-64 Two doses on days 0, 28 IM HI≥40 (after 2 doses) =
58% (90µg)
43% (45µg)
26% (15µg)
17% (7.5µg)		 HI≥4 fold increase (after 2 doses) =
57% (90µg)
41% (45µg)
24% (15µg)
13% (7.5µg)		 Fold increase in HI (after two doses) = 4.5 (90µg)
3.1 (45µg)
1.7 (15µg)
1.3 (7.5µg)		 2005-2006 New Eng. J. Med, 2006, 13, 1343-1351
*** (J.Treanor)		 Trial conducted by NIAID
Inactivated split virus Sanofi Pasteur, USA H5N1 A/Vietnam/1203/2004 Egg Al(OH)3 3.75, 7.5, 15, 45 I/II 600 >65 Two doses on days 0 and 28 IM HI≥40 ( after 2 doses) =
37% (45µg+Alum)
16% (15µg+Alum)
19% (7.5µg+Alum)
16% (3.75µg+Alum)
36% (45µg no Alum)
29% (15µg no Alum)
22% (7.5µg no Alum)
6% (3.75µg no Alum) 		HI≥4 fold increase (after 2 doses) =
33% (45µg+Al)
14% (15µg+Al)
12% (7.5µg+Al)
8% (3.75µg+Al)
34% (45µg no Alum)
21% (15µg no Alum)
15% (7.5µg no Alum)
6% (3.75µg no Alum) 		No data 2006-2007 Abstract* (R. Brady) Trial conducted by NIAID
Inactivated split virus Sanofi Pasteur, USA H5N1 A/Vietnam/1203/2004 Egg None 45 I/II 125 Child:2-9 years Two doses on days 0 and 28 with 3rd dose option IM After 2 doses:
HI>40 = 38%
NT>40 =84%		 After 2 doses ≥4 fold increse in:
HI = 38%
NT = 59% 		After two doses fold increase in:
HI = 3.4
NT = 8.0 		2006-2007 Abstract *(I. Graham) *** (J. Campbel) Slightly better responses in 6-9 year olds compared to 2-5 years olds. Trial conducted by NIAID
Inactivated split virus Sanofi Pasteur, USA H5N1 A/Vietnam/1203/2004 Egg Al(OH)3 3.75, 7.5, 15, 45 I 600 Adult Two doses on days 0, 28 IM HI≥40 ( after 2 doses) =
33% (45µg+Al)
15% (15µg+Al)
14% (7.5µg+Al)
2% (3.75µg+Al)
26% (45µg no Alum)
13% (15µg no Alum)
0% (7.5µg no Alum)
4% (3.75µg no Alum) 		HI≥4 fold increase (after 2 doses) =
33% (45µg+Al)
14% (15µg+Al)
14% (7.5µg+Al)
2% (3.75µg+Al)
25% (45µg no Alum)
13% (15µg no Alum)
0% (7.5µg no Alum)
4% (3.75µg no Alum) 		HI fold increase (after 2 doses) =
2.8 (45µg+Alum)
1.6 (15µg+Alum)
1.5 (7.5µg+Alum)
1.1 (3.75µg+Aum)
2.3 (45µg no Alum)
1.6 (15µg no Alum)
1.1 (7.5µg no Alum)
1.1 (3.75µg no Alum) 		2006-2007 Abstract *** (W. Keitel) Significant beneficial effect of Aluminium hydroxide was not observed
Inactivated split virus Sanofi Pasteur, USA H5N1 A/Vietnam/1203/2004 Egg None 3, 9 I 100 18-40 Two doses on days 0, 28 with boosting 7 months after second dose ID HI≥40 (after 3 doses) =
25% (9µg)
15% (3µg) 		HI≥>4 fold increase (after 3 doses) =
25% (9µg)
15% (3µg) 		HI fold increase (after 3 doses) =
2.1 (9µg)
1.6 (3µg) 		2005-2006 Abstract *** (W. Keitel) A clinical trial comparing 30µg given ID or IM is scheduled to begin in 2007 Trial conducted by NIAID
Inactivated split virus Sanofi Pasteur, USA H5N1 A/Vietnam/1203/2004 Egg None 15, 45 I 100 18-40 Two doses on days 0, 28 with boosting 7 months after second dose IM HI≥40 (after 3 doses) =
62% (45µg)
13% (15µg)		 H≥4 fold increase (after 3 doses) =
62% (45µg)
6% (15µg)		 HI fold increase (after 3 doses) =
7.2 (45µg)
1.9 (15µg)		 2005-2006 *** (W. Keitel) A clinical trial comparing 30µg given ID or IM is scheduled to begin in 2007 Trial conducted by NIAID
Inactivated split virus Sanofi Pasteur, USA H5N1 A/HK/156/97, Protein Sciences baculovirus purified HA (clade 3) - priming A/VN/1203/04 (clade 1) boosting Egg None 90 boosting 37 18-64 Boosting: single dose in H5 primed subjects, two doses in H5 naive group IM HI≥40 (after 1 dose) = 70% HI≥4 fold increase (after 1 dose) = 68% HI fold increase (after 1 dose) = 12.3 Priming in 1998 boosting in 2005 Abstract *** (J. Treanor)
Inactivated subunit Microgen, Russia H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 15, 30, 45 I 120 18-50 Two doses on days 0, 28 IM HI≥40 (after 2 doses) =
43% (45 µg+Alum)
21% (30µg+Alum) 50%(15µg+Alum) 		HI≥4 fold increase (after 2 doses) =
78% (45 µg+Alum)
44% (30µg+Alum)
78% (15µg+Alum)		 Fold increase in HI =
5.6 (45µg+Alum)
2.7 (30µg+Alum)
5.3(15µg+Alum) 		2006-2007 Abstract *** (I. Krasilnikov)
Inactivated subunit Microgen, Russia H5N1 A/Vietnam/1194/2004 Egg polyoxidonium 15, 30, 45 I 120 18-50 Two doses on days 0, 28 IM HI≥40 =
51% (45 µg+Alum)
29% (30µg+Alum) 36%(15µg+Alum) 		HI≥4 fold increase =
77% (45 µg+Alum)
58% (30µg+Alum)
49%(15µg+Alum)		 Fold increase in HI =
5.3 (45µg+Alum)
3.3 (30µg+Alum)
3.1 (15µg+Alum) 		2006-2007 Abstract *** (I. Krasilnikov)
Inactivated subunit Novartis V&D, Italy H5N3 A/duck/Singapore/1997 Egg MF59 7.5, 15, 30 I 65 18-40 Two doses on days 0, 21 followed by boosting 16 months after second dose IM SRH>25 (after 2 doses) = 100% (all doses+MF59)
36% (30µg no MF59)
45% (15µg no MF59)
0% (7.5µg no MF59) 		NT≥4 fold increase after grouping all doses adjuvanted or non-adjuvanted vaccines =
100%(with MF59) 3 doses
64%(with MF59) 2 doses
18% (no MF59) 3 doses
0%( no MF59) 2 doses 		Fold increse in SRH (after 2 doses) = 18.0 (30µg+MF59)
19.0 (15µg+MF59)
23.0 (7.5µg+MF59)
2.3 (30µg no MF59)
3.1 (15µg no MF59)
1.0 (7.5 no MF59) 		1999-2000 (completed) Lancet 2001, 357,1937-43 MF59 significantly increased titres of antibodies and cross-reactivity with H5N1 viruses.

Vaccine 2003, 21, 1687-93
J Infect Dis 2005,191,1210-1215
Inactivated subunit Novartis V&D, Italy H9N2 A/Hong Kong/1073/99 Egg MF59 3.75, 7.5, 15, 30 I/II 96 18-34 Two doses on days 0, 28 IM HI>32 (after 2 doses) =
100% (30µg+MF59)
100% (15µg+MF59)
92% (7.5µg+MF59)
100% (3.75µg+MF59)
75% (30µg, no MF59)
50% (15µg no MF59)
58% (7.5µg no MF59)
67% (3.75 no MF59)		 HI≥4 fold increase (after 2 doses) =
100% (30µg+MF59)
100% (15µg+MF59)
92% (7.5µg+MF59)
92% (3.75µg+MF59)
67% (30µg, no MF59)
50% (15µg no MF59)
50% (7.5µg no MF59)
67% (3.75µg no MF59)		 Fold increase in HI (after 2 doses) = 28.2 (30µg+MF59)
18.0 (15µg+MF59)
18.0 (7.5µg+MF59)
27.0 (3.75µg+MF59)
5.0 (30µg, no MF59)
3.8 (15µg no MF59)
3.2 (7.5µg no MF59)
5.3 (3.75 no MF59)		 2005 (completed) Clin. Infect Dis. 2006,43, 1135-1142
* (R.Atmar)		 Effects of MF59 were more evident after 2 doses.

Trial conducted by NIAID.

EMEA: Centrally authorised pandemic influenza 'mock-up' vaccines on 2 May 2007 Trade mark: Focetria
Inactivated subunit Novartis V&D, Italy H5N1 A/Vietnam/1203/2004 Egg None 15, 30, 45 I/II 390 18-64 Two doses on days 0, 28 IM NI≥40 (after 2 doses) =
29% (45µg)
18% (30µg)
24% (15µg) 		NI≥4 fold increase (after 2 doses) =
26% (45µg)
18% (30µg)
17% (15µg) 		Fold increase in HI (after 2 doses) = 3.0 (45µg)
2.1 (30µg)
1.8 (7.5µg)		 2006 Abstract *** (D. Bernstein) Effects of MF59 were more evident after 2 doses.
Trial conducted by NIAID
Inactivated subunit Novartis V&D, Italy H5N1 A/Vietnam/1203/2004 Egg Al(OH)3 7.5, 15, 30 I/II 390 18-64 Two doses on days 0, 28 IM HI≥40 (after 2 doses) =
14% (30µg)
7% (15µg)
3% (7.5µg) 		HI≥4 fold increase (after 2 doses) =
14% (30µg)
7% (15µg)
3% (7.5µg) 		Fold increase in HI (after 2 doses) = 1.8 (30µg)
1.4 (15µg)
1.2 (7.5µg) 		2006 Abstract *** (D. Bernstein) Effects of MF59 were more evident after 2 doses.
Trial conducted by NIAID
Inactivated subunit Novartis V&D, Italy H5N1 A/Vietnam/1203/2004 Egg MF59 7.5, 15 I/II 390 18-64 Two doses on days 0,28 IM HI≥40 (after 2 doses) =
63% (15µg)
23% (7.5mg)		 HI≥4 fold increase (after 2 doses) =
56% (15µg)
23% (7.5mg)		 Fold increase in HI (after 2 doses) = 5.8 (15µg)
2.7 (7.5µg) 		2006 Abstract *** (D. Bernstein) Effects of MF59 were more evident after 2 doses.
Trial conducted by NIAID
Inactivated subunit Novartis V&D, Italy H5N1 A/Vietnam/1194/2004 Egg MF59 7.5, 15 II 321 18-60 Two doses on days 0, 21 IM Results not publicly available Results not publicly available Results not publicly available 2006 *** (A. Banhoff)  
Inactivated subunit Novartis V&D, Italy H5N1 A/Vietnam/1194/2004 Egg MF59 7.5, 15 II 173 >60 Two doses on days 0, 21 IM Results not publicly available Results not publicly available Results not publicly available 2006 *** (A. Banhoff)
Inactivated subunit Novartis V&D, Italy H5N3 H3N2
B		 A/Duck/Singapoore/97 A/Panama/2007/99 B/Guandong/120/2000 Egg LTK63 7.5 I 100 18-40 Two doses on days 1, 7 IN No data on mucoprotection ≥2.5 fold increase of mucosal HI Ab in volunteers given 30 µg LTK63+BV =

IgA IgG  
47% 21% (H5N3)
53% 17% (H3N2)
93% 40% (B)
Fold increase of mucosal Ab in volunteers given 30µgLTK63+BV in ELISA =
IgA IgG  
3.3 2.0 (H5N3)
2.3 1.9 (H3N2)
6.3 3.5 (B)
2002 (completed) J. Virol. 2006, 80, 10, 4962-4970
Inactivated subunit Novartis V&D, Italy H5N3 H3N2
B		 A/Duck/Singapoore/97 A/Panama/2007/99 B/Guandong/120/2000 Egg MF59 15 I 100 18-40 Two doses on days 1, 21 IM No data on mucoprotection ≥2.5 fold increase of mucosal HI Ab in volunteers given MF59 =

IgA IgG  
10% 80% (H5N3)
10% 60% (H3N2)
20% 33% (B)

Fold increase of mucosal Ab in volunteers given MF59 in ELISA =

IgA IgG  
1.8 15.5 (H5N3)
1.4 3.9 (H3N2)
2.1 10.1 (B)
2002 (completed) J. Virol. 2006, 80, 10, 4962-4970
Inactivated subunit Novartis V&D, Italy H5N1 A/Vietnam/1194/2004 Egg MF59 7.5, 15 II app.250 >18 Two doses followed by a 6 month booster dose IM No data No data No data Start 2006 No data
Inactivated subunit Solvay Pharmaceuticals, Netherlands H5N1 A/Vietnam/1194/2004 Egg Al(OH)3 10, 30 I 400 18-49 Two doses on days 0, 21 IM No data No data No data Start 2007 No data
Inactivated subunit Solvay Pharmaceuticals, Netherlands H5N1 A/Vietnam/1194/2004 MDCK cells Al(OH)3 To be determined I To be determined 18-49 To be determined IM No data No data No data Start 2007 No data
Live attenuated Medimmune, USA H5N1 A/Vietnam/1203/2004 x A/AnnArbor/6/60 ca Egg None 106.7TCID50 I 18 18 -49 Two doses on days 1, 28 IN No data HI≥4 fold increase = 11% No data Start 2006 Abstract *** (R. Karron) Collaborative project under CRADA with NIAID
Live attenuated Medimmune, USA H5N1 A/Vietnam/1203/2004 x A/AnnArbor/6/60 ca Egg None 107.5TCID50 I 21 (2nd dose pending) 18 -49 Two doses on days 1, 28 IN No data No data No data Start 2007 Abstract *** (R. Karron) Collaborative project under CRADA with NIAID
Live attenuated Medimmune, USA H5N1 A/HongKong/213/2003 x A/AnnArbor/6/60 ca Egg None 107.5TCID50 I 22 18 -49 Two doses on days 1, 28 IN No data No data No data Start 2007 No data
Live attenuated Novavax, USA H9N2 A/Chicken/HongKong/G9/97 x A/AnnArbor/6/60 ca Egg None 107 TCID50 I 24 >18 & born after 1968 Two doses on days 1, 28 IN No data HI ≥4 fold increase = 92% in seronegative subjects No data Start 2006 Abstract** (K. Subbarao) Collaborative project under CRADA with NIAID
Live attenuated Inst. of Experimental Medicine, Russia H5N2 Reassortant A/17/Duck/Potsdam/88/92 (H5N2) x Len 17 (H2N2) Egg None 107.5TCID50 I 20 18-25 Two doses on days 0, 21 IN HI≥40 =
Blood
11% (1 dose)
29% (2 doses)		 HI≥4 fold increase in HI:
Blood sIgA =  
6% 30% (1 dose)
47% 65% (2 doses)
Fold increase in HI:
Blood sIgA =  
1.3 1.7 (1 dose)
2.8 2.8 (2 doses)
2006 Abstract*** (L. Rudenko) Two doses induce antibody cross reacting with highly pathogenic H5N1 strains
Recombinant Merck & Co. Inc, USA Identical for many subtypes M2 protein Cell No data No data I No data Adult No data No data No data No data No data Start 2006 No data
Recombinant Protein Sciences, USA H5N1 Baculovirus expressed HA from viruses A/Hong Kong/156/97 (HK/156) and A/Hong Kong/483/97 (HK/483) Insect cells None 25, 45, 90, 90+10 I/II 147 Adult Two doses IM NT≥80 =
52% (90µg)
33% (90µg+10µg)
28% (45µg)
17% (25µg) 		No data No data 1999-2000 (completed) Vaccine, 2001, 19, 1732-1737
Recombinant Cytos Biotechnology, Switzerland Identical for many subtypes M2 protein E. coli VLP 100 1 40 Adult Two doses SC No data No data No data Start:2008 No data
DNA vaccine NIH, USA H5N1 DNA plasmid encoding H5, Indonesian strain Plasmid None None 1 45 Adult Three doses with 1 month intervals IM No data No data No data 2006-2008 *** G. Nabel

IM - intramuscular, SC - subcutaneous, IN - intranasal, ID - intradermal, VLP - virus like particles, HI -hemagglutination inhibition, NT - neutralization, SRH - single radial haemolysis, sIgA - secretory IgA antibody, PO -polyoxidonium
& - Average data from three Japanese manufacturers
 
* Materials of the WHO meeting on evaluation of pandemic influenza vaccines in clinical trials, 2-3 Nov 2005, Geneva
http://www.who.int/vaccine_research/diseases/influenza/mtg_021205/en/index.html
 
** Materials of the 2nd WHO meeting on evaluation of pandemic vaccines in clinical trials, 4-5 May 2006, Geneva
http://www.who.int/vaccine_research/diseases/influenza/meeting_040506/en/index.html

*** Materials of the 3rd WHO meeting on evaluation of pandemic vaccines in clinical trials, 15-16 February 2007, Geneva
http://www.who.int/vaccine_research/diseases/influenza/meeting_150207/en/index.html

Tables on the Clinical trials of pandemic influenza prototype vaccines: 1,2,3,4