Tweet
http://www.telegraph.co.uk/news/news...even-days.html
Vaccine can protect against bird flu in seven days
A new vaccine could offer protection against bird flu in just one week, instead of the usual six.
By Kate Devlin Medical Correspondent
Last Updated: 1:09AM BST 09 Oct 2008
Tests by researchers at University Hospitals Leicester show that 80 per cent of people were immune within seven days of having the new vaccine Photo: REUTERS
The "primer" jab can be given up to eight years before an outbreak and needs only a "booster" injection to innoculate fully.
Scientists behind the development believe that it could offer quicker protection against potentially fatal avian influenza, if the disease begins to spread rapidly around the world.
Conventional vaccination requires two jabs, four weeks apart, and a wait of another two weeks for immunity.
Tests by researchers at University Hospitals Leicester show that 80 per cent of people were immune within seven days of taking the second "booster" vaccine, roughly the same number as with the more traditional approach.
Dr Iain Stephenson, who led the study, said: "With the pre-priming approach you could choose certain groups in advance, for instance health care workers, and almost vaccinate at leisure. Then you would only a need a week to provide protection."
The second vaccine contains the bird flu strain H5N1, while the first uses a strain known as H5N3.
Around 60 patients were tested including some who had been given the earlier vaccination between 1999 and 2001, as part of a previous study.
The early findings, included in a letter to the New England Journal of Medicine, show that after one week 80 per cent of those already "primed" were protected, compared to 20 per cent of those in the other group.
Dr Stephenson said that although the Government was already stockpiling a bird flu vaccine it wasn't yet obvious how people would be offered the jabs if the disease began to spread suddenly.
"People need two vaccinations a month apart and there is a further two weeks before protective antibodies (defence cells) build up," he said.
"If a bird flu pandemic erupted tomorrow it isn't clear we would have six weeks to vaccinate people before it arrived in this country, even if the vaccine was stockpiled. We have been able to prove in this study that you can vaccinate people six, seven or eight years ago and still get a very rapid response with a booster shot within a week."
letter from new england J of med
</td> </tr><tr> <td> <table width="100%" bgcolor="#ffffff" border="0" cellpadding="2" cellspacing="0"> <tbody><tr valign="top"><td colspan="2"></td></tr> <tr valign="top"><td valign="top" width="15" align="center">
</td><td valign="middle"> PDF</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">PDA Full Text</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Supplementary Material</td></tr> <tr valign="top"><td colspan="2"></td></tr> </tbody></table> </td> </tr> <tr> <td width="200" align="center" bgcolor="#e8e8d1">
</td> </tr> <tr> <td> <table width="100%" bgcolor="#ffffff" border="0" cellpadding="2" cellspacing="0"> <tbody><tr valign="top"><td colspan="2"></td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Add to Personal Archive</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Add to Citation Manager</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Notify a Friend</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">E-mail When Cited</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">E-mail When Letters Appear</td></tr> <tr valign="top"><td colspan="2"></td></tr> </tbody></table> </td> </tr> <tr> <td width="200" align="center" bgcolor="#e8e8d1">
</td> </tr> <tr> <td> <table width="100%" bgcolor="#ffffff" border="0" cellpadding="2" cellspacing="0"> <tbody><tr valign="top"><td colspan="2"></td></tr> <tr valign="top"><td colspan="2"></td></tr> </tbody></table> </td> </tr> </tbody></table> </td></tr></tbody></table> <!-- end of outer content box1 --> <!-- end of outer content box2 --> <!-- TEXT --> <!-- <CENTER> Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1
</CENTER> --> To the Editor: Antigenically distinct avian influenza A (H5N1)<sup> </sup>viruses are widely dispersed.<sup>1</sup> Clade 1 H5N1 viruses previously<sup> </sup>predominated in Indochina. Indonesian, Eurasian, and African<sup> </sup>viruses are clustered in a clade 2 group, with antigenically<sup> </sup>distinct sublineages. Clade 0 viruses caused influenza outbreaks<sup> </sup>in Hong Kong in 1997 but have not been isolated since then.<sup> </sup>To reduce shortfalls in vaccine supply at the onset of the next<sup> </sup>pandemic, advance stockpiling of vaccine has been suggested.<sup> </sup>Because of antigenic evolution of H5N1, current vaccines may<sup> </sup>be suboptimally matched to the actual pandemic virus. Proactive<sup> </sup>priming may induce immune memory, allowing low-dose vaccination<sup> </sup>to induce rapid cross-protection when needed.<sup> </sup>
We report on an open-label study conducted from June through<sup> </sup>August 2007 at Leicester Royal Infirmary, Leicester, United<sup> </sup>Kingdom (for details, see the Supplementary Appendix, available<sup> </sup>with the full text of this letter at www.nejm.org). Two 7.5-µg<sup> </sup>doses of MF59-adjuvanted, surface-antigen vaccine against clade<sup> </sup>1 A/Vietnam/1194/2004 (NIBRG-14) (Novartis) were administered<sup> </sup>by intramuscular injection 21 days apart to subjects who had<sup> </sup>been vaccinated (primed) with clade 0 H5 vaccine at least 6<sup> </sup>years earlier. All primed subjects had received two doses of<sup> </sup>either MF59-adjuvanted or nonadjuvanted (plain) A/duck/Singapore/97<sup> </sup>(H5N3) vaccine containing 7.5 to 30 µg of hemagglutinin<sup> </sup>in studies conducted between 1999 and 2001.<sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>4</sup> Some subjects<sup> </sup>had also received a booster dose 16 months after primary immunization.<sup>3</sup><sup> </sup>Antibody responses were detected with the use of neutralizing<sup> </sup>and hemagglutination-inhibition assays performed at the U.K.<sup> </sup>Health Protection Agency, with homologous clade 1 NIBRG-14 and<sup> </sup>heterologous clade 2.2 NIBRG-23 vaccine reference strains and<sup> </sup>by hemagglutination-inhibition assay at the Centers for Disease<sup> </sup>Control and Prevention with wild-type A/Vietnam/1194/2004 (clade<sup> </sup>1), A/Indonesia/5/2005 (clade 2.1), A/Anhui/1/2005 (clade 2.3),<sup> </sup>and A/Turkey/15/2006 (clade 2.2) viruses (see the Supplementary Appendix<sup> </sup>for details).<sup> </sup>
Twenty-four subjects had received two or three doses of either<sup> </sup>plain or MF59-adjuvanted H5N3 vaccine, with subjects equally<sup> </sup>divided between the two groups. Thirty subjects were unprimed.<sup> </sup>Vaccines had acceptable side-effect profiles, and no serious<sup> </sup>vaccine-related adverse events were recorded. Serum samples<sup> </sup>were obtained immediately before each of the two doses of vaccine<sup> </sup>was administered (on days 0 and 21) and on days 7, 14, and 42<sup> </sup>after vaccination.<sup> </sup>
On each post-vaccination day, and with each assay, geometric<sup> </sup>mean titers of antibodies to NIBRG-14 and NIBRG-23 were significantly<sup> </sup>higher among the primed subjects than among the unprimed subjects<sup> </sup>(P<0.001 for all comparisons, except on day 42 for NIBRG-14<sup> </sup>on hemagglutination-inhibition assay). From day 14 onward, and<sup> </sup>for each assay, titers of antibodies to both viruses were significantly<sup> </sup>higher in the MF59-primed group than in the plain-primed group<sup> </sup>(P<0.05 for all comparisons). The highest titers were observed<sup> </sup>on day 14 in the MF59-primed group, with geometric mean titers<sup> </sup>of antibodies to NIBRG-14 and NIBRG-23 of 1:378 and 1:347, respectively,<sup> </sup>on hemagglutination-inhibition assay and of 1:1754 and 1:2128,<sup> </sup>respectively, on neutralizing assay (Figure 1 and the Supplementary Appendix).<sup> </sup>No relation between the post-vaccination titer and the number<sup> </sup>of previous doses of H5N3 vaccine or their antigen content was<sup> </sup>observed. By day 7, at least 80% of MF59-primed subjects had<sup> </sup>titers of at least 1:40 for all wild-type viruses tested on<sup> </sup>hemagglutination-inhibition assay.<sup> </sup>
<!-- null --> <table cellpadding="0" cellspacing="0"><tbody><tr bgcolor="#e8e8d1"><td><table cellpadding="2" cellspacing="2"><tbody><tr bgcolor="#e8e8d1"><td valign="top" align="center" bgcolor="#ffffff">
View larger version (32K):
<nobr>[in this window]
[in a new window]
</nobr> </td><td valign="top" align="left"> Figure 1. Titers of Antibodies to NIBRG-14 and NIBRG-23 and Reverse Cumulative Distribution Curves on Day 7 after One Dose of Vaccine. Shown are geometric mean (log<sub>10</sub>) titers (GMT) of antibodies to A/Vietnam/1194/2004 (NIBRG-14) (Panel A) and A/turkey/Turkey/1/2005 (NIBRG-23) (Panel B), as determined by hemagglutination-inhibition (HAI) assay, after the administration of two doses of vaccine 21 days apart. Responses are shown for 30 subjects who had not previously received H5 influenza vaccine (unprimed subjects), 12 subjects who had been primed with nonadjuvanted (plain) H5 vaccine, and 12 subjects who had been primed with MF59-adjuvanted H5 vaccine. Reverse cumulative distribution curves at day 7 after one dose of vaccine are shown for subjects who had been primed with either MF59-adjuvanted H5 vaccine (Panel C) or plain H5 vaccine (Panel D). The percentage of subjects with an HAI titer is based on the total number of samples available. Antibody titers are shown for four wild-type H5 viruses: A/Vietnam/1194/2004, A/Indonesia/5/2005, A/Anhui/1/2005, and A/Turkey/15/2006. Ind denotes Indonesia, and VN Vietnam.
</td></tr></tbody></table></td></tr></tbody></table>
Modeling of pandemic spread shows that the maximum reduction<sup> </sup>in viral transmission is achieved by the induction of a response<sup> </sup>within 2 weeks after the outbreak of the pandemic.<sup>5</sup> Because<sup> </sup>two doses of the vaccine are required, rapid vaccine deployment<sup> </sup>will be challenging. Our findings indicate that priming subjects<sup> </sup>with H5 antigen induces a rapidly mobilized, long-lasting immune<sup> </sup>memory after the administration of low-dose, antigenically distinct<sup> </sup>vaccine. Given the protective titers detected by day 7, the<sup> </sup>effect of MF59 adjuvant is striking. Consideration could be<sup> </sup>given to a proactive vaccine-priming strategy, particularly<sup> </sup>among those at high risk for pandemic influenza such as health<sup> </sup>care workers, so that cross-clade antibodies could be rapidly<sup> </sup>generated after single vaccination or after exposure to the<sup> </sup>pandemic virus.
Vaccine can protect against bird flu in seven days
A new vaccine could offer protection against bird flu in just one week, instead of the usual six.
By Kate Devlin Medical Correspondent
Last Updated: 1:09AM BST 09 Oct 2008
Tests by researchers at University Hospitals Leicester show that 80 per cent of people were immune within seven days of having the new vaccine Photo: REUTERS The "primer" jab can be given up to eight years before an outbreak and needs only a "booster" injection to innoculate fully.
Scientists behind the development believe that it could offer quicker protection against potentially fatal avian influenza, if the disease begins to spread rapidly around the world.
Conventional vaccination requires two jabs, four weeks apart, and a wait of another two weeks for immunity.
Tests by researchers at University Hospitals Leicester show that 80 per cent of people were immune within seven days of taking the second "booster" vaccine, roughly the same number as with the more traditional approach.
Dr Iain Stephenson, who led the study, said: "With the pre-priming approach you could choose certain groups in advance, for instance health care workers, and almost vaccinate at leisure. Then you would only a need a week to provide protection."
The second vaccine contains the bird flu strain H5N1, while the first uses a strain known as H5N3.
Around 60 patients were tested including some who had been given the earlier vaccination between 1999 and 2001, as part of a previous study.
The early findings, included in a letter to the New England Journal of Medicine, show that after one week 80 per cent of those already "primed" were protected, compared to 20 per cent of those in the other group.
Dr Stephenson said that although the Government was already stockpiling a bird flu vaccine it wasn't yet obvious how people would be offered the jabs if the disease began to spread suddenly.
"People need two vaccinations a month apart and there is a further two weeks before protective antibodies (defence cells) build up," he said.
"If a bird flu pandemic erupted tomorrow it isn't clear we would have six weeks to vaccinate people before it arrived in this country, even if the vaccine was stockpiled. We have been able to prove in this study that you can vaccinate people six, seven or eight years ago and still get a very rapid response with a booster shot within a week."
letter from new england J of med
Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1
<table width="200" align="right" border="0" cellpadding="0" cellspacing="0"> <tbody><tr> <td width="20"> </td> <td bgcolor="#336699"> <table border="0" cellpadding="0" cellspacing="1"> <tbody><tr valign="top"> <td width="200" align="center" bgcolor="#e8e8d1"></td> </tr><tr> <td> <table width="100%" bgcolor="#ffffff" border="0" cellpadding="2" cellspacing="0"> <tbody><tr valign="top"><td colspan="2"></td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle"> PDF</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">PDA Full Text</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Supplementary Material</td></tr> <tr valign="top"><td colspan="2"></td></tr> </tbody></table> </td> </tr> <tr> <td width="200" align="center" bgcolor="#e8e8d1"></td> </tr> <tr> <td> <table width="100%" bgcolor="#ffffff" border="0" cellpadding="2" cellspacing="0"> <tbody><tr valign="top"><td colspan="2"></td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Add to Personal Archive</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Add to Citation Manager</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">Notify a Friend</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">E-mail When Cited</td></tr> <tr valign="top"><td valign="top" width="15" align="center"></td><td valign="middle">E-mail When Letters Appear</td></tr> <tr valign="top"><td colspan="2"></td></tr> </tbody></table> </td> </tr> <tr> <td width="200" align="center" bgcolor="#e8e8d1"></td> </tr> <tr> <td> <table width="100%" bgcolor="#ffffff" border="0" cellpadding="2" cellspacing="0"> <tbody><tr valign="top"><td colspan="2"></td></tr> <tr valign="top"><td colspan="2"></td></tr> </tbody></table> </td> </tr> </tbody></table> </td></tr></tbody></table> <!-- end of outer content box1 --> <!-- end of outer content box2 --> <!-- TEXT --> <!-- <CENTER> Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1</CENTER> --> To the Editor: Antigenically distinct avian influenza A (H5N1)<sup> </sup>viruses are widely dispersed.<sup>1</sup> Clade 1 H5N1 viruses previously<sup> </sup>predominated in Indochina. Indonesian, Eurasian, and African<sup> </sup>viruses are clustered in a clade 2 group, with antigenically<sup> </sup>distinct sublineages. Clade 0 viruses caused influenza outbreaks<sup> </sup>in Hong Kong in 1997 but have not been isolated since then.<sup> </sup>To reduce shortfalls in vaccine supply at the onset of the next<sup> </sup>pandemic, advance stockpiling of vaccine has been suggested.<sup> </sup>Because of antigenic evolution of H5N1, current vaccines may<sup> </sup>be suboptimally matched to the actual pandemic virus. Proactive<sup> </sup>priming may induce immune memory, allowing low-dose vaccination<sup> </sup>to induce rapid cross-protection when needed.<sup> </sup>
We report on an open-label study conducted from June through<sup> </sup>August 2007 at Leicester Royal Infirmary, Leicester, United<sup> </sup>Kingdom (for details, see the Supplementary Appendix, available<sup> </sup>with the full text of this letter at www.nejm.org). Two 7.5-µg<sup> </sup>doses of MF59-adjuvanted, surface-antigen vaccine against clade<sup> </sup>1 A/Vietnam/1194/2004 (NIBRG-14) (Novartis) were administered<sup> </sup>by intramuscular injection 21 days apart to subjects who had<sup> </sup>been vaccinated (primed) with clade 0 H5 vaccine at least 6<sup> </sup>years earlier. All primed subjects had received two doses of<sup> </sup>either MF59-adjuvanted or nonadjuvanted (plain) A/duck/Singapore/97<sup> </sup>(H5N3) vaccine containing 7.5 to 30 µg of hemagglutinin<sup> </sup>in studies conducted between 1999 and 2001.<sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>4</sup> Some subjects<sup> </sup>had also received a booster dose 16 months after primary immunization.<sup>3</sup><sup> </sup>Antibody responses were detected with the use of neutralizing<sup> </sup>and hemagglutination-inhibition assays performed at the U.K.<sup> </sup>Health Protection Agency, with homologous clade 1 NIBRG-14 and<sup> </sup>heterologous clade 2.2 NIBRG-23 vaccine reference strains and<sup> </sup>by hemagglutination-inhibition assay at the Centers for Disease<sup> </sup>Control and Prevention with wild-type A/Vietnam/1194/2004 (clade<sup> </sup>1), A/Indonesia/5/2005 (clade 2.1), A/Anhui/1/2005 (clade 2.3),<sup> </sup>and A/Turkey/15/2006 (clade 2.2) viruses (see the Supplementary Appendix<sup> </sup>for details).<sup> </sup>
Twenty-four subjects had received two or three doses of either<sup> </sup>plain or MF59-adjuvanted H5N3 vaccine, with subjects equally<sup> </sup>divided between the two groups. Thirty subjects were unprimed.<sup> </sup>Vaccines had acceptable side-effect profiles, and no serious<sup> </sup>vaccine-related adverse events were recorded. Serum samples<sup> </sup>were obtained immediately before each of the two doses of vaccine<sup> </sup>was administered (on days 0 and 21) and on days 7, 14, and 42<sup> </sup>after vaccination.<sup> </sup>
On each post-vaccination day, and with each assay, geometric<sup> </sup>mean titers of antibodies to NIBRG-14 and NIBRG-23 were significantly<sup> </sup>higher among the primed subjects than among the unprimed subjects<sup> </sup>(P<0.001 for all comparisons, except on day 42 for NIBRG-14<sup> </sup>on hemagglutination-inhibition assay). From day 14 onward, and<sup> </sup>for each assay, titers of antibodies to both viruses were significantly<sup> </sup>higher in the MF59-primed group than in the plain-primed group<sup> </sup>(P<0.05 for all comparisons). The highest titers were observed<sup> </sup>on day 14 in the MF59-primed group, with geometric mean titers<sup> </sup>of antibodies to NIBRG-14 and NIBRG-23 of 1:378 and 1:347, respectively,<sup> </sup>on hemagglutination-inhibition assay and of 1:1754 and 1:2128,<sup> </sup>respectively, on neutralizing assay (Figure 1 and the Supplementary Appendix).<sup> </sup>No relation between the post-vaccination titer and the number<sup> </sup>of previous doses of H5N3 vaccine or their antigen content was<sup> </sup>observed. By day 7, at least 80% of MF59-primed subjects had<sup> </sup>titers of at least 1:40 for all wild-type viruses tested on<sup> </sup>hemagglutination-inhibition assay.<sup> </sup>
<!-- null --> <table cellpadding="0" cellspacing="0"><tbody><tr bgcolor="#e8e8d1"><td><table cellpadding="2" cellspacing="2"><tbody><tr bgcolor="#e8e8d1"><td valign="top" align="center" bgcolor="#ffffff">
View larger version (32K):
<nobr>[in this window]
[in a new window]
</nobr> </td><td valign="top" align="left"> Figure 1. Titers of Antibodies to NIBRG-14 and NIBRG-23 and Reverse Cumulative Distribution Curves on Day 7 after One Dose of Vaccine. Shown are geometric mean (log<sub>10</sub>) titers (GMT) of antibodies to A/Vietnam/1194/2004 (NIBRG-14) (Panel A) and A/turkey/Turkey/1/2005 (NIBRG-23) (Panel B), as determined by hemagglutination-inhibition (HAI) assay, after the administration of two doses of vaccine 21 days apart. Responses are shown for 30 subjects who had not previously received H5 influenza vaccine (unprimed subjects), 12 subjects who had been primed with nonadjuvanted (plain) H5 vaccine, and 12 subjects who had been primed with MF59-adjuvanted H5 vaccine. Reverse cumulative distribution curves at day 7 after one dose of vaccine are shown for subjects who had been primed with either MF59-adjuvanted H5 vaccine (Panel C) or plain H5 vaccine (Panel D). The percentage of subjects with an HAI titer is based on the total number of samples available. Antibody titers are shown for four wild-type H5 viruses: A/Vietnam/1194/2004, A/Indonesia/5/2005, A/Anhui/1/2005, and A/Turkey/15/2006. Ind denotes Indonesia, and VN Vietnam.
</td></tr></tbody></table></td></tr></tbody></table>
Modeling of pandemic spread shows that the maximum reduction<sup> </sup>in viral transmission is achieved by the induction of a response<sup> </sup>within 2 weeks after the outbreak of the pandemic.<sup>5</sup> Because<sup> </sup>two doses of the vaccine are required, rapid vaccine deployment<sup> </sup>will be challenging. Our findings indicate that priming subjects<sup> </sup>with H5 antigen induces a rapidly mobilized, long-lasting immune<sup> </sup>memory after the administration of low-dose, antigenically distinct<sup> </sup>vaccine. Given the protective titers detected by day 7, the<sup> </sup>effect of MF59 adjuvant is striking. Consideration could be<sup> </sup>given to a proactive vaccine-priming strategy, particularly<sup> </sup>among those at high risk for pandemic influenza such as health<sup> </sup>care workers, so that cross-clade antibodies could be rapidly<sup> </sup>generated after single vaccination or after exposure to the<sup> </sup>pandemic virus.
Comment