Giuseppe
Emeritus
[From European Centre of Diseases Prevention and Control (ECDC) Website: http://www.ecdc.europa.eu/en/Health_Topics/influenza/news/news_Influenza_080828.aspx]
SCIENTIFIC ADVANCES ? AVIAN INFLUENZA- VACCINES
Human H5N1 Vaccines
28th August 2008
-- Immune responses of healthy subjects to a single does of intramuscular inactivated influenza A(H5N1) after priming with an antigenic variant.
Goji et al. JID 2008: 198: 635-641 (http://www.ncbi.nlm.nih.gov/pubmed/18694338?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
-- An adjuvanted, low-dose, pandemic influenza A(H5N1) vaccine candidate is safe, immunogenic and induces cross-reactive immune responses in health adults.
Levie et al. JID 2008; 198: 642-649 (http://www.ncbi.nlm.nih.gov/pubmed/18576945?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
-- Editorial Commentary: Vaccines against Influenza A (H5N1): Evidence of Progress
Poland G.A. and Sambhara S. JID 2008; 198: 629-631 (http://www.ncbi.nlm.nih.gov/pubmed/18694337?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Descriptions:
These two studies and the accompanying editorial published in a one issue of the Journal of Infectious Diseases add to the published information concerning human avian influenza vaccines (often referred to as ?pre-pandemic vaccines?).
The study by Goji et al investigated the possible effectiveness of the prime-boost strategy.
Two groups of subjects were challenged (injected) in 2006 with a single dose of a vaccine based on a recent clade of A(H5N1).
One group had received two doses of a vaccine based on an early clade of influenza A(H5N1) in 1998.
The other group had never been exposed to A(H5N1).
The researchers found a good response to even the single dose in 2006 in those that had been immunised in 1998, even among two thirds of those that had been classified as non-responders to the 1998 vaccine.(1)
The work by Levie et al looked at whether oil-in-water adjuvants increased the effectiveness of a split-virion A(H5N1) vaccine and whether the vaccine produced reasonable serological cross-immunoreactivity against a range of challenges with different viruses.
The workers found that even very low doses of the adjuvanted vaccine (1.9 μg) good response against the injected strain and some level of cross-reactivity against different strains.(2)
The accompanying editorial commentary gives some interesting perspectives on potential implications from the on-going developments in A(H5N1) vaccine technology and understanding. (3)
ECDC Comment (28/08/08):
The prime-boost strategy is based on the concept that eventually avian influenza viruses type A(H5N1) change to a form of that is better adapted to humans than is the case now and so results in a human pandemic.(3)
Then it is hoped that immunisation ahead of time by a vaccine based on one type of influenza A(H5N1) ? the priming, means that only one boosting injection would be needed with a more specific vaccine when the pandemic comes.
Normally two injections separated by an interval are needed to get good protection when trying to protect humans against a novel influenza.
The adjuvant findings are important as they will potentially allow dose-sparing.
This is crucial as vaccines specific to the pandemic strain will not be available for some months after the pandemic starts and when they start to arrive they will be in short supply.
Dose-sparing means that many more people will be immunised from a fixed amount of vaccine.
Finally the cross-reactivity suggests that even if the specific pandemic strain has drifted away from the strains that have been used in the vaccines some protection may be obtained.
These results are encouraging as they support the reality of cross-clade A(H5N1) immunoreactivity after vaccination, dose-sparing and a prime-boost phenomenon across H5 clades following much earlier administration of human A(H5N1) vaccines.
Following recommendations from its Advisory Forum in 2006, ECDC convened two expert panels in 2006 that reviewed published and unpublished data and produced guidance for EU member states on A(H5N1) human avian influenza vaccines.(4)
Looking at whether they were likely to give some protection (with the conclusion they would)(5) and when and where they might be used.(6)
No recommendations could be given on whether to purchase these vaccine because its not in ECDC?s mandate to do so.
However the decision over whether to purchase and give these vaccines is especially difficult for countries.
The difficulty of the decision both reflects the lack of any certainty over the inevitability of an A(H5) pandemic and the high cost of the vaccines.
Some European countries are investing, others are not.
It has been noted recently that the Japanese are reported to be immunising numbers of people with these vaccines.
However as pointed out by ECDC in May this is a pragmatic decision rather than a policy development.(7)
The Japanese authorities have had these vaccines for some time and they were approaching their expiry date. Rather than let them go to waste a decision was made to offer them to around 6000 people at higher occupation risk and government workers. This means some invaluable information will come from Japan in 2009.
Where caution has to be expressed is the level of protection that will be achieved.
Cross-immunoreactivity (immunisation with one protein inducing antibodies that react against another related protein) implies but does not guarantee cross-protection (actual protection of human recipients against infection and disease from the pandemic strain).
Also the level of protection cannot be certain until the pandemic comes.
Though modelling work suggests even a low protection is of public health value there will be public disappointment with a vaccine that perhaps delivers protection that is less than 50% effective in any individual.(8)
While the case for these vaccines is stronger whether to purchase them remains a difficult decision.
?1.Goji NA, Nolan C, Hill H et al (2008) Immune responses of healthy subjects to a single does of intramuscular inactivated influenza A(H5N1) after priming with an antigenic variant. JID 2008: 198: 635-641
?2.Levie K, Leroux-Roels I, Hoppenbrouers K et al (2008). An adjuvanted, low-dose, pandemic influenza A(H5N1) vaccine candidate is safe, immunogenic and induces cross-reactive immune responses in health adults. JID 2008; 198: 642-9
?Poland G.A. and Sambhara S. (2008) Editorial Commentary: Vaccines against Influenza A (H5N1): Evidence of Progress, JID 2008; JID, 198: 629-631.
?ECDC Risk Assessment on H5N1.The public health risk from highly pathogenic avian influenza viruses emerging in Europe with specific reference to influenza type A/H5N1.
http://www.ecdc.eu.int/Health_topics/Avian_Influenza/pdf/060601_public_health_risk_HPAI.pdf
?5. Influenza team (ECDC). Human influenza A/H5N1 (?pre-pandemic?) vaccines: informing policy development in Europe. Euro Surveill. 2007;12(38)
ii=3272. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3272
?6.ECDC Technical report: Conclusion of the Expert Advisory Groups on human H5N1 vaccines- Scientific Questions. Stockholm, August 2007. (http://ecdc.europa.eu/pdf/Sci Questions final.pdf)
?7.ECDC Technical report: Conclusion of the Expert Advisory Groups on human H5N1 vaccines- Public Health and Operational Questions. Stockholm, August 2007
(http://ecdc.europa.eu/pdf/PH Questions final.pdf)
?8. ECDC Influenza News April 24th; Japanese Ministry of Health to initiate large vaccination trial of human A(H5N1) avian influenza vaccine in health care and emergency response workers. (http://ecdc.europa.eu/en/Health_Topics/influenza/news/news_Influenza_080424.aspx#Public2)
?9.Ferguson NM (2006), Cummings DA, Fraser C, Cajka JC, Cooley PC, Burke DS.Strategies for mitigating an influenza pandemic Nature 2006 Jul 27;442(7101):448-52. Epub 2006 Apr 26; doi:10.1038/nature04795
-
Comment to influenza@ecdc.europa.eu
--------
SCIENTIFIC ADVANCES ? AVIAN INFLUENZA- VACCINES
Human H5N1 Vaccines
28th August 2008
-- Immune responses of healthy subjects to a single does of intramuscular inactivated influenza A(H5N1) after priming with an antigenic variant.
Goji et al. JID 2008: 198: 635-641 (http://www.ncbi.nlm.nih.gov/pubmed/18694338?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
-- An adjuvanted, low-dose, pandemic influenza A(H5N1) vaccine candidate is safe, immunogenic and induces cross-reactive immune responses in health adults.
Levie et al. JID 2008; 198: 642-649 (http://www.ncbi.nlm.nih.gov/pubmed/18576945?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
-- Editorial Commentary: Vaccines against Influenza A (H5N1): Evidence of Progress
Poland G.A. and Sambhara S. JID 2008; 198: 629-631 (http://www.ncbi.nlm.nih.gov/pubmed/18694337?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Descriptions:
These two studies and the accompanying editorial published in a one issue of the Journal of Infectious Diseases add to the published information concerning human avian influenza vaccines (often referred to as ?pre-pandemic vaccines?).
The study by Goji et al investigated the possible effectiveness of the prime-boost strategy.
Two groups of subjects were challenged (injected) in 2006 with a single dose of a vaccine based on a recent clade of A(H5N1).
One group had received two doses of a vaccine based on an early clade of influenza A(H5N1) in 1998.
The other group had never been exposed to A(H5N1).
The researchers found a good response to even the single dose in 2006 in those that had been immunised in 1998, even among two thirds of those that had been classified as non-responders to the 1998 vaccine.(1)
The work by Levie et al looked at whether oil-in-water adjuvants increased the effectiveness of a split-virion A(H5N1) vaccine and whether the vaccine produced reasonable serological cross-immunoreactivity against a range of challenges with different viruses.
The workers found that even very low doses of the adjuvanted vaccine (1.9 μg) good response against the injected strain and some level of cross-reactivity against different strains.(2)
The accompanying editorial commentary gives some interesting perspectives on potential implications from the on-going developments in A(H5N1) vaccine technology and understanding. (3)
ECDC Comment (28/08/08):
The prime-boost strategy is based on the concept that eventually avian influenza viruses type A(H5N1) change to a form of that is better adapted to humans than is the case now and so results in a human pandemic.(3)
Then it is hoped that immunisation ahead of time by a vaccine based on one type of influenza A(H5N1) ? the priming, means that only one boosting injection would be needed with a more specific vaccine when the pandemic comes.
Normally two injections separated by an interval are needed to get good protection when trying to protect humans against a novel influenza.
The adjuvant findings are important as they will potentially allow dose-sparing.
This is crucial as vaccines specific to the pandemic strain will not be available for some months after the pandemic starts and when they start to arrive they will be in short supply.
Dose-sparing means that many more people will be immunised from a fixed amount of vaccine.
Finally the cross-reactivity suggests that even if the specific pandemic strain has drifted away from the strains that have been used in the vaccines some protection may be obtained.
These results are encouraging as they support the reality of cross-clade A(H5N1) immunoreactivity after vaccination, dose-sparing and a prime-boost phenomenon across H5 clades following much earlier administration of human A(H5N1) vaccines.
Following recommendations from its Advisory Forum in 2006, ECDC convened two expert panels in 2006 that reviewed published and unpublished data and produced guidance for EU member states on A(H5N1) human avian influenza vaccines.(4)
Looking at whether they were likely to give some protection (with the conclusion they would)(5) and when and where they might be used.(6)
No recommendations could be given on whether to purchase these vaccine because its not in ECDC?s mandate to do so.
However the decision over whether to purchase and give these vaccines is especially difficult for countries.
The difficulty of the decision both reflects the lack of any certainty over the inevitability of an A(H5) pandemic and the high cost of the vaccines.
Some European countries are investing, others are not.
It has been noted recently that the Japanese are reported to be immunising numbers of people with these vaccines.
However as pointed out by ECDC in May this is a pragmatic decision rather than a policy development.(7)
The Japanese authorities have had these vaccines for some time and they were approaching their expiry date. Rather than let them go to waste a decision was made to offer them to around 6000 people at higher occupation risk and government workers. This means some invaluable information will come from Japan in 2009.
Where caution has to be expressed is the level of protection that will be achieved.
Cross-immunoreactivity (immunisation with one protein inducing antibodies that react against another related protein) implies but does not guarantee cross-protection (actual protection of human recipients against infection and disease from the pandemic strain).
Also the level of protection cannot be certain until the pandemic comes.
Though modelling work suggests even a low protection is of public health value there will be public disappointment with a vaccine that perhaps delivers protection that is less than 50% effective in any individual.(8)
While the case for these vaccines is stronger whether to purchase them remains a difficult decision.
?1.Goji NA, Nolan C, Hill H et al (2008) Immune responses of healthy subjects to a single does of intramuscular inactivated influenza A(H5N1) after priming with an antigenic variant. JID 2008: 198: 635-641
?2.Levie K, Leroux-Roels I, Hoppenbrouers K et al (2008). An adjuvanted, low-dose, pandemic influenza A(H5N1) vaccine candidate is safe, immunogenic and induces cross-reactive immune responses in health adults. JID 2008; 198: 642-9
?Poland G.A. and Sambhara S. (2008) Editorial Commentary: Vaccines against Influenza A (H5N1): Evidence of Progress, JID 2008; JID, 198: 629-631.
?ECDC Risk Assessment on H5N1.The public health risk from highly pathogenic avian influenza viruses emerging in Europe with specific reference to influenza type A/H5N1.
http://www.ecdc.eu.int/Health_topics/Avian_Influenza/pdf/060601_public_health_risk_HPAI.pdf
?5. Influenza team (ECDC). Human influenza A/H5N1 (?pre-pandemic?) vaccines: informing policy development in Europe. Euro Surveill. 2007;12(38)
ii=3272. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3272?6.ECDC Technical report: Conclusion of the Expert Advisory Groups on human H5N1 vaccines- Scientific Questions. Stockholm, August 2007. (http://ecdc.europa.eu/pdf/Sci Questions final.pdf)
?7.ECDC Technical report: Conclusion of the Expert Advisory Groups on human H5N1 vaccines- Public Health and Operational Questions. Stockholm, August 2007
(http://ecdc.europa.eu/pdf/PH Questions final.pdf)
?8. ECDC Influenza News April 24th; Japanese Ministry of Health to initiate large vaccination trial of human A(H5N1) avian influenza vaccine in health care and emergency response workers. (http://ecdc.europa.eu/en/Health_Topics/influenza/news/news_Influenza_080424.aspx#Public2)
?9.Ferguson NM (2006), Cummings DA, Fraser C, Cajka JC, Cooley PC, Burke DS.Strategies for mitigating an influenza pandemic Nature 2006 Jul 27;442(7101):448-52. Epub 2006 Apr 26; doi:10.1038/nature04795
-
Comment to influenza@ecdc.europa.eu
--------