Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate
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{"title"=>"Optimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate", "type"=>"journal", "authors"=>[{"first_name"=>"Steven", "last_name"=>"Riley", "scopus_author_id"=>"7102619416"}, {"first_name"=>"Joseph T.", "last_name"=>"Wu", "scopus_author_id"=>"7409256423"}, {"first_name"=>"Gabriel M.", "last_name"=>"Leung", "scopus_author_id"=>"7007159841"}], "year"=>2007, "source"=>"PLoS Medicine", "identifiers"=>{"sgr"=>"34347257116", "doi"=>"10.1371/journal.pmed.0040218", "pui"=>"46998621", "pmid"=>"17579511", "scopus"=>"2-s2.0-34347257116", "issn"=>"15491277", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)"}, "id"=>"33614282-a1f3-3d08-9dda-143aa7e0726e", "abstract"=>"BACKGROUND: 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.\\n\\nMETHODS 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.\\n\\nCONCLUSIONS: 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.", "link"=>"http://www.mendeley.com/research/optimizing-dose-prepandemic-influenza-vaccines-reduce-infection-attack-rate", "reader_count"=>57, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>9, "Researcher"=>13, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>2, "Professor"=>8}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>9, "Researcher"=>13, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>2, "Professor"=>8}, "reader_count_by_subject_area"=>{"Unspecified"=>9, "Agricultural and Biological Sciences"=>13, "Business, Management and Accounting"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Computer Science"=>1, "Decision Sciences"=>1, "Engineering"=>1, "Environmental Science"=>1, "Mathematics"=>5, "Medicine and Dentistry"=>17, "Physics and Astronomy"=>1, "Psychology"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Social Sciences"=>{"Social Sciences"=>2}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>5}, "Unspecified"=>{"Unspecified"=>9}, "Environmental Science"=>{"Environmental Science"=>1}, "Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "United States"=>3, "Taiwan"=>1, "Denmark"=>1, "United Kingdom"=>3, "Australia"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/475876", "https://ndownloader.figshare.com/files/475924", "https://ndownloader.figshare.com/files/475961", "https://ndownloader.figshare.com/files/475995", "https://ndownloader.figshare.com/files/476041"], "description"=>"<div><h3>Background</h3><p>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.</p> <h3>Methods and Findings</h3><p>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.</p> <h3>Conclusions</h3><p>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.</p> </div>", "links"=>[], "tags"=>["optimizing", "pre-pandemic", "influenza", "vaccines"], "article_id"=>153757, "categories"=>["Cancer", "Biotechnology"], "users"=>["Steven Riley", "Joseph T Wu", "Gabriel M Leung"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.0040218.sd001", "https://dx.doi.org/10.1371/journal.pmed.0040218.sd002", "https://dx.doi.org/10.1371/journal.pmed.0040218.sg001", "https://dx.doi.org/10.1371/journal.pmed.0040218.sg002", "https://dx.doi.org/10.1371/journal.pmed.0040218.st001"], "stats"=>{"downloads"=>12, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Optimizing_the_Dose_of_Pre_Pandemic_Influenza_Vaccines_to_Reduce_the_Infection_Attack_Rate/153757", "title"=>"Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-06-19 01:02:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/948412"], "description"=>"<p>Vaccine candidates were those reported by (A) Treanor et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b006\" target=\"_blank\">6</a>] (on day 56 after the initial dose), (B) Bresson et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b004\" target=\"_blank\">4</a>] (day 42, with alum) and (C) Lin et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b005\" target=\"_blank\">5</a>] (day 42). The legends show the range of doses included in the clinical trial for each vaccine. The y-axis shows the reverse cumulative proportion of participants with HI titres (x-axis). Each titre level constitutes an immune state <i>h<sub>i</sub></i>. We assume that <i>p<sub>T</sub>(h<sub>i</sub>;x<sub>j</sub>)</i> is equal to the logarithmic interpolation between the discrete doses (see main text).</p>", "links"=>[], "tags"=>["Infectious diseases", "public health and epidemiology", "Virology"], "article_id"=>618747, "categories"=>["Infectious Diseases", "Virology", "Biotechnology"], "users"=>["Steven Riley", "Joseph T Wu", "Gabriel M Leung"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0040218.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Individual_Level_Vaccine_Response_for_Three_Vaccine_Candidates_/618747", "title"=>"Individual-Level Vaccine Response for Three Vaccine Candidates", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-06-19 02:25:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/948648"], "description"=>"<p>Vaccine candidates were those reported by Treanor et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b006\" target=\"_blank\">6</a>] (red); Bresson et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b004\" target=\"_blank\">4</a>] (blue); and Lin et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b005\" target=\"_blank\">5</a>] (green). For comparison, the dose (x-axis) is given as a proportion of the maximum dose used in the clinical trial. The range of doses used for each vaccine is indicated in the legend.</p>", "links"=>[], "tags"=>["susceptibility", "vaccination"], "article_id"=>618973, "categories"=>["Infectious Diseases", "Virology", "Biotechnology"], "users"=>["Steven Riley", "Joseph T Wu", "Gabriel M Leung"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0040218.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expected_Reduction_in_Susceptibility_after_Vaccination_z_for_the_Three_Vaccines_/618973", "title"=>"Expected Reduction in Susceptibility after Vaccination 〈<i>z</i>〉 for the Three Vaccines", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-06-19 02:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/948571"], "description"=>"<div><p>(A) Treanor et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b006\" target=\"_blank\">6</a>].</p>\n <p>(B) Bresson et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b004\" target=\"_blank\">4</a>].</p>\n <p>(C) Lin et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b005\" target=\"_blank\">5</a>].</p>\n <p>The underlying level of transmission <i>β</i> was calculated so as to maintain the same attack rate as the homogeneous model with <i>R</i><sub>0</sub> = 1.8, i.e., 73%. The blue lines and dots on the chart describe results for optimal policies, with doses at or very close to the minimum tested range, as calculated using the homogeneous model. The red lines and dots describe results for a restricted policy, i.e., the dose used had to be large enough to provide an expected reduction in the susceptibility of an individual of 〈<i>z</i>〉 = 0.4 (see <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-g004\" target=\"_blank\">Figure 4</a>). Solid lines (not perfectly vertical) show the predicted reduction in infection attack rate for the homogeneous model, i.e., relative infectivity α = 0 and relative susceptibility <i>ε</i> = 0. The dashed lines show the benefit of the two different policies with relative infectivity of the risk group twice that of the rest of the population, i.e., <i>α</i> = 1, and relative susceptibility twice that of the rest of the population, i.e., <i>ε</i> = 1. Dots show the results from 1,000 Latin-hypercube samples [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b027\" target=\"_blank\">27</a>] over the linear range for <i>α</i> and <i>ε,</i> and the log range of the x-axes for stockpile size. The red and blue vertical lines show the stockpile size at which complete coverage of the high-risk group is first achieved. The vertical black line shows the smallest stockpile size at which the whole population can be offered the optimal dose.</p></div>", "links"=>[], "tags"=>["inclusion", "high-risk", "children"], "article_id"=>618907, "categories"=>["Infectious Diseases", "Virology", "Biotechnology"], "users"=>["Steven Riley", "Joseph T Wu", "Gabriel M Leung"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0040218.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sensitivity_of_Predicted_Reduction_in_Attack_Rate_to_the_Inclusion_of_a_High_Risk_Group_Representing_Children_for_Three_Vaccine_Candidates_/618907", "title"=>"Sensitivity of Predicted Reduction in Attack Rate to the Inclusion of a High-Risk Group Representing Children for Three Vaccine Candidates", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-06-19 02:28:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/948487"], "description"=>"<div><p>Vaccines candidates were those reported by (A, D) Treanor et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b006\" target=\"_blank\">6</a>]; (B, E) Bresson et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b004\" target=\"_blank\">4</a>]; and (C, F) Lin et al. [<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040218#pmed-0040218-b005\" target=\"_blank\">5</a>].</p>\n <p>(A–C) Infection attack rate <i>a</i> (colour as per legend) for different dosing strategies (y-axes) and different stockpile sizes (antigen per capita, x-axes). The solid black line shows the optimal dosing strategy at which the infection attack rate is minimized. Note that where the thick black line is not horizontal; it corresponds to (antigen per capita) = 2 × (dose). This is because each individual requires two doses of vaccine.</p>\n <p>(D–F) Illustration of the relationship between optimal coverage (proportion of population receiving vaccine, green lines, right y-axes) and optimal dose (blue lines, left y-axes) for different stockpile sizes (antigen per capita, x-axes).</p></div>", "links"=>[], "tags"=>["dosing", "strategies"], "article_id"=>618827, "categories"=>["Infectious Diseases", "Virology", "Biotechnology"], "users"=>["Steven Riley", "Joseph T Wu", "Gabriel M Leung"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0040218.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_Alternative_Dosing_Strategies_for_the_Three_Vaccines_/618827", "title"=>"Impact of Alternative Dosing Strategies for the Three Vaccines", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-06-19 02:27:07"}

PMC Usage Stats | Further Information

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Relative Metric

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