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Article: Optimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate
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TitleOptimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate
 
AuthorsRiley, S1
Wu, JT1
Leung, GM1
 
Issue Date2007
 
PublisherPublic Library of Science. The Journal's web site is located at http://medicine.plosjournals.org/perlserv/?request=index-html&issn=1549-1676
 
CitationPlos Medicine, 2007, v. 4 n. 6, p. 1032-1040 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pmed.0040218
 
AbstractBackground: The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile. Methods and Findings: We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible. Conclusions: In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall. © 2007 Riley et al.
 
ISSN1549-1277
 
DOIhttp://dx.doi.org/10.1371/journal.pmed.0040218
 
PubMed Central IDPMC1892041
 
ISI Accession Number IDWOS:000247476300016
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorRiley, S
 
dc.contributor.authorWu, JT
 
dc.contributor.authorLeung, GM
 
dc.date.accessioned2012-02-17T06:12:51Z
 
dc.date.available2012-02-17T06:12:51Z
 
dc.date.issued2007
 
dc.description.abstractBackground: The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile. Methods and Findings: We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible. Conclusions: In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall. © 2007 Riley et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos Medicine, 2007, v. 4 n. 6, p. 1032-1040 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pmed.0040218
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pmed.0040218
 
dc.identifier.epage1040
 
dc.identifier.hkuros128678
 
dc.identifier.isiWOS:000247476300016
 
dc.identifier.issn1549-1277
 
dc.identifier.issue6
 
dc.identifier.pmcidPMC1892041
 
dc.identifier.pmid17579511
 
dc.identifier.scopuseid_2-s2.0-34347257116
 
dc.identifier.spage1032
 
dc.identifier.urihttp://hdl.handle.net/10722/144858
 
dc.identifier.volume4
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://medicine.plosjournals.org/perlserv/?request=index-html&issn=1549-1676
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS Medicine
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCommunicable Disease Control - methods
 
dc.subject.meshDisease Outbreaks - prevention and control
 
dc.subject.meshInfluenza Vaccines - administration and dosage - immunology
 
dc.subject.meshInfluenza in Birds - immunology
 
dc.subject.meshInfluenza, Human - immunology
 
dc.titleOptimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong