Optimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate.
Optimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate.
复制标题
DOI：
10.1371/journal.pmed.0040218
复制
发表时间：
2007-06
期刊：
影响因子：
15.8
通讯作者：
Leung GM
中科院分区：
文献类型：
--
作者：
Riley S;Wu JT;Leung GM
最近禽流感在野生鸟类和家禽中的传播可能是出现类似1918年人类大流行的前兆。因此，正在考虑储存人类大流行前疫苗（针对禽类毒株）。对许多国家来说，这些疫苗储备的主要制约因素将是维持抗原的总质量。我们检验了这样一种假设，即较低的个人剂量（即低于获得最大保护的推荐剂量）可能会提供大量额外的社区效益，因为它们将允许在给定的抗原储存总量下扩大疫苗覆盖范围。我们使用数学模型来预测不同政策下的感染率。该模型既包括个体对不同剂量疫苗接种的反应，也包括大流行性流感在人与人之间传播的过程。我们发现，如果以较低剂量给更多的人接种疫苗，可能会大幅降低发病率。这些结果适用于所有可获得数据的三种候选疫苗。作为对影响程度的指导，我们基于免疫原性的历史研究模拟了流行病。例如，对于有数据的一种疫苗，如果美国3亿总人口中有160人获得最佳剂量，而不是3亿人中有20人获得最大保护剂量（如美国国家大流行防范计划所公布的），则发病率将从67.6%降至58.7%。关于疫苗保护的确切性质，我们的结果是保守的。我们还考虑了一个模型变体，其中包括一个代表儿童的高风险亚组。对于允许仅以最佳剂量向高危人群提供疫苗的较小储备规模，在存在风险群体的情况下，使用同质模型的预测效益形成了一个下限，即使高风险群体的传染性和易感性是前者的两倍。除了个人层面的保护（即疫苗效力）外，在决定储备规模和剂量时，还应考虑大流行前疫苗计划对人群水平的影响。我们的研究结果表明，为了增加人口覆盖率，降低疫苗剂量可能是合理的，从而降低总体感染发病率。Steven Riley和他的同事们研究了“延长”有限的疫苗供应的潜在好处，并建议如果以较低的剂量给更多的人接种疫苗，就有可能大幅降低发病率。每年冬天，数百万人感染流感，这是一种鼻子、喉咙和呼吸道的病毒感染。大多数人恢复得很快，但这种疾病可能是致命的。在美国，季节性流感爆发（流行病）每年造成36000多人死亡。现在，人们担心禽流感病毒可能引发人类流感大流行——一种可能导致数百万人死亡的全球流行病。季节性流行病的发生是因为流感病毒不断地对其血凝素和神经氨酸酶分子（免疫系统识别的病毒蛋白（抗原））进行微小的改变。由于这种“抗原漂移”，免疫系统的反应（可以通过感染流感或接种残废的流感病毒株引起）在今年对抗流感，但在明年可能只能提供部分保护。“抗原转移”（流感抗原的巨大变化）可能导致大流行，因为社区对变化后的病毒没有免疫力。禽流感病毒含有一种血凝素类型，与目前流行的人类流感病毒不同，虽然禽流感病毒引起了一些人类流感病例，但由于它不能在人与人之间轻易传播，尚未引发人类大流行。如果它获得这种特性，可能会涉及进一步的小抗原变化，在科学家开发出有效的疫苗之前，它可能会杀死数百万人。为了提供一些临时保护，许多国家正在储备针对禽流感病毒的“大流行前”疫苗。例如，美国计划储存足够的大流行前疫苗，为其3亿人口中的2000万人（包括关键卫生工作者）提供最大限度的保护。但是，鉴于流感大流行前的疫苗储备有限，让更多的人接种较低剂量的疫苗，这可能会减少易受感染的人数，并通过防止流感病毒的有效传播诱导群体免疫，从而成为限制流感大流行传播的更好方法吗？在这项研究中，研究人员使用数学模型来调查这个问题。为了预测与不同疫苗接种政策相关的感染率，这组科学家开发了一个数学模型，该模型结合了三种针对禽流感病毒的实验性疫苗诱导的人类免疫反应数据和以前大流行性流感病毒人际传播的历史数据。该模型预测，对于所有疫苗，给更多的人注射低剂量疫苗比给更少的人注射高剂量疫苗能更好地限制流感的传播。例如，这组科学家估计，如果把美国计划储备的一种实验性疫苗平均分配给1.6亿人，而不是按完全保护剂量给2000万人接种，可能会在不到一年的时间里避免大约2700万例流感病例。然而，向900万美国卫生保健工作者提供最大保护剂量，并在普通人群中使用较低剂量的剩余疫苗以优化保护，可能只能避免1400万例感染。这些发现表明，鉴于大流行前疫苗的储备有限，通过使用低剂量疫苗来增加疫苗接种的人口覆盖率，可能比为更少的人接种完全保护性剂量的疫苗更有效地降低总体流感感染率。然而，由于研究人员的模型包含了许多假设，它只能给出不同策略可能如何执行的指示，而不是每种策略可能避免多少流感病例的确定数字。在公共卫生官员使用这个或类似的模型来帮助他们决定使用大流行前疫苗来控制人类流感大流行的最佳方式之前，他们将需要更多关于这些疫苗效力和当前流行病毒传播率的信息。他们还需要知道大流行前疫苗是否像本研究中假设的那样，实际上提供了对大流行病毒的良好保护，然后才能建议使用低剂量大流行前疫苗进行大规模免疫接种、使用高剂量选择性疫苗接种或采用混合策略。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0040218访问这些网站。美国疾病控制和预防中心为患者和卫生专业人员提供有关流感和流感疫苗接种的信息（英文、西班牙文、菲律宾文、中文和越南文）。世界卫生组织有一份关于流感和全球应对禽流感的情况说明书(英文、西班牙文、法文、俄文、阿拉伯文、MedlinePlus在线百科全书有一个关于流感的页面（英语和西班牙语）英国卫生保护局关于禽流感、大流行流感和季节性流感的信息美国国家过敏和传染病研究所有一个名为“关注流感”的综合功能
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. 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. 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. Steven Riley and colleagues examine the potential benefits of "stretching" a limited supply of vaccine and suggest that substantial reductions in the attack rate are possible if vaccines are given to more people at lower doses. Every winter, millions of people catch influenza, a viral infection of the nose, throat, and airways. Most recover quickly, but the disease can be deadly. In the US, seasonal influenza outbreaks (epidemics) cause 36,000 excess deaths annually. And now there are fears that an avian (bird) influenza virus might trigger a human influenza pandemic—a global epidemic that could kill millions. Seasonal epidemics occur because flu viruses continually make small changes to their hemagglutinin and neuraminidase molecules, the viral proteins (antigens) that the immune system recognizes. Because of this “antigenic drift,” an immune system response (which can be induced by catching flu or by vaccination with disabled circulating influenza strains) that combats flu one year may provide only partial protection the next year. “Antigenic shift” (large changes in flu antigens) can cause pandemics because communities have no immunity to the changed virus. Although avian influenza virus, which contains a hemagglutinin type that differs from currently circulating human flu viruses, has caused a few cases of human influenza, it has not started a human pandemic yet because it cannot move easily between people. If it acquires this property, which will probably involve further small antigenic changes, it could kill millions of people before scientists can develop an effective vaccine against it. To provide some interim protection, many countries are preparing stockpiles of “pre-pandemic” vaccines targeted against the avian virus. The US, for example, plans to store enough pre-pandemic vaccine to provide maximum protection to 20 million people (including key health workers) out of its population of 300 million. But, given a limited stockpile of pre-pandemic vaccine, might giving more people a lower dose of vaccine, which might reduce the number of people susceptible to infection and induce herd immunity by preventing efficient transmission of the flu virus, be a better way to limit the spread of pandemic influenza? In this study, the researchers have used mathematical modeling to investigate this question. To predict the infection rates associated with different vaccination policies, the researchers developed a mathematical model that incorporates data on human immune responses induced with three experimental vaccines against the avian virus and historical data on the person–person transmission of previous pandemic influenza viruses. For all the vaccines, the model predicts that giving more people a low dose of the vaccine would limit the spread of influenza better than giving fewer people the high dose needed for full individual protection. For example, the researchers estimate that dividing the planned US stockpile of one experimental vaccine equally between 160 million people instead of giving it at the fully protective dose to 20 million people might avert about 27 million influenza cases in less than year. However, giving the maximally protective dose to the 9 million US health-care workers and using the remaining vaccine at a lower dose to optimize protection within the general population might avert only 14 million infections. These findings suggest that, given a limited stockpile of pre-pandemic vaccine, increasing the population coverage of vaccination by using low doses of vaccine might reduce the overall influenza infection rate more effectively than vaccinating fewer people with fully protective doses of vaccine. However, because the researchers' model includes many assumptions, it can only give an indication of how different strategies might perform, not firm numbers for how many influenza cases each strategy is likely to avert. Before public-health officials use this or a similar model to help them decide the best way to use pre-pandemic vaccines to control a human influenza pandemic, they will need more information about the efficacy of these vaccines and about transmission rates of currently circulating viruses. They will also need to know whether pre-pandemic vaccines actually provide good protection against the pandemic virus, as assumed in this study, before they can recommend mass immunization with low doses of pre-pandemic vaccine, selective vaccination with high doses, or a mixed strategy. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040218. US Centers for Disease Control and Prevention provide information on influenza and influenza vaccination for patients and health professionals (in English, Spanish, Filipino, Chinese, and Vietnamese) The World Health Organization has a fact sheet on influenza and on the global response to avian influenza (in English, Spanish, French, Russian, Arabic, and Chinese) The MedlinePlus online encyclopedia devotes a page to flu (in English and Spanish) The UK Health Protection Agency information on avian, pandemic, and seasonal influenza The US National Institute of Allergy and Infectious Diseases has a comprehensive feature called “focus on the flu”
登录
查看更多内容
影响因子：
5
作者：
Hannoun, C;Megas, F;Piercy, J
通讯作者：
Piercy, J
影响因子：
2
作者：
Cauchemez, S;Carrat, F;Boëlle, PY
通讯作者：
Boëlle, PY
影响因子：
158.5
作者：
Treanor, JJ;Campbell, JD;Wolff, M
通讯作者：
Wolff, M
影响因子：
64.8
作者：
Taubenberger, JK;Reid, AH;Fanning, TG
通讯作者：
Fanning, TG
影响因子：
168.9
作者：
Lin, Jiangtao;Zhang, Jiansan;Yin, Weidong
通讯作者：
Yin, Weidong