Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.
Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.
复制标题
SARS-COV-2疫苗给药方案的流行病学和进化考虑。
DOI：
10.1126/science.abg8663
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发表时间：
2021-04-23
期刊：
影响因子：
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通讯作者：
Wagner CE
中科院分区：
文献类型：
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作者：
Saad-Roy CM;Morris SE;Metcalf CJE;Mina MJ;Baker RE;Farrar J;Holmes EC;Pybus OG;Graham AL;Levin SA;Grenfell BT;Wagner CE
对于预防严重急性呼吸综合征冠状病毒2型的两剂疫苗，一些司法管辖区已决定推迟第二剂疫苗的接种，以迅速让更多人接种疫苗。偏离制造商规定的剂量方案的后果尚不清楚，但将取决于对疫苗的免疫反应的强度。Saad-Roy等人采用建模方法来解决疫苗推出所面临的不可避免的不确定性。作者发现，虽然单剂量策略通常在短期内减少感染，但从长期来看，结果取决于免疫的稳健性。如果免疫反应不理想，病毒在一些接种疫苗的人群中继续复制，可能导致免疫逃逸突变，单剂量策略可能会增加抗原进化的可能性。至关重要的是收集接种者的血清学数据，并在世界范围内加强疫苗接种工作，以避免不良后果。在某些情况下，单剂量疫苗政策可能会增加病毒抗原进化的可能性。随着严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）大流行的持续，部署安全有效的疫苗是减轻疾病严重程度和传播的关键干预措施。在国际上分发核准疫苗的同时，也出现了许多后勤方面的挑战和短缺。为此，一些国家选择推迟第二剂接种，以努力增加至少接受一剂接种的人数。因此，一个关键问题就变成了第二剂注射的时间将如何影响未来的流行病学和进化结果。我们建立在现有的免疫流行病学框架的基础上，该框架假设，如果不接种疫苗，从原发性感染恢复后的个体免疫力可能最终减弱，导致对继发性感染的易感性（可能降低）。为了探索流行病学结果，我们扩展了模型，纳入了两个接种疫苗的类别，对应于接种了一剂或两剂SARS-CoV-2疫苗的个体。与自然免疫一样，我们允许一剂或两剂疫苗免疫减弱，并且我们考虑在两次疫苗之间的剂量期间有一个连续的频谱。为了反映由于第二次剂量延迟而导致的有效剂量的增加，我们将第一次剂量的给药率建模为剂量间隔时间的增加函数。然后，我们通过将该框架与不同进化情景下潜在病毒适应的简单系统动力学模型相结合来考虑进化结果，每种进化情景都有自己的关于病毒丰度和不同部分易感类的宿主内选择的假设。我们发现，延迟第二次疫苗剂量可以通过增加免疫个体的比例在短期内减少COVID-19感染。然而，从长期来看，感染负担和病毒适应的相对潜力高度依赖于自然或疫苗免疫反应的稳健性。值得注意的是，我们发现，即使单剂疫苗产生的免疫力很差，也可以从早期的一剂政策开始，以增加免疫个体的数量，然后随着疫苗容量的增加而转向制造商推荐的两剂方案，以减轻潜在的长期负面流行病学和进化结果。随着可用性的提高，也可以通过提高总体疫苗接种率来实现这种缓解。SARS-CoV-2疫苗的部署将有力地塑造大流行后的流行病学轨迹和人群累积免疫的特征。我们的模型表明，在中期内，不同的疫苗剂量制度和自然免疫和疫苗免疫的稳健性差异的组合可能导致广泛的潜在流行病学和进化结果。因此，必须通过仔细的临床评估来确定临床保护和传播阻断免疫的强度和持续时间，以便执行健全的公共政策。在疫苗部署延迟和疫苗接种率低的地方，我们的研究结果强调了随后可能出现的负面流行病学和进化影响。特别是因为这些后果（例如，新变种的演变）可能成为全球性问题，因此迫切需要在疫苗分配和部署方面实现全球公平。使用免疫流行病学模型（左）和系统动力学模型（中）来探索中期对COVID-19感染负担和免疫景观（右上）以及SARS-CoV-2病毒适应的潜在比率（右下）的预测。随附的在线交互式应用程序（http://grenfelllab.princeton.edu/sarscov2vaccine）可用于为广泛的模型参数探索这些预测。鉴于疫苗剂量短缺和后勤方面的挑战，正在提出各种部署战略，以提高人口对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的免疫水平。出现了两个关键问题：第二次剂量的递送时间将如何影响感染动力学，以及它将如何影响病毒免疫通过部分免疫个体的积累而进化的前景。两者都取决于与自然免疫和两剂免疫相比，单剂免疫引起的免疫反应的稳健性。在现有的免疫流行病学模型的基础上，我们发现，在短期内，专注于一次剂量通常会减少感染，但长期结果取决于这种相对的免疫稳健性。然后，我们探索了三种选择情景，并发现在某些群体部分免疫的条件下，单剂量政策可能会增加抗原性进化的潜力。我们强调迫切需要在一次疫苗剂量后测试病毒载量和量化免疫反应，并在全球范围内加强疫苗接种工作。
For two-dose vaccines against severe acute respiratory syndrome coronavirus 2, some jurisdictions have decided to delay the second dose to rapidly get the vaccine into more people. The consequences of deviating from manufacturer-prescribed dosing regimens are unknown but will depend on the strength of immune responses to the vaccines. Saad-Roy et al. took a modeling approach to tackling the inevitable uncertainties facing vaccine rollout. The authors found that although one-dose strategies generally reduce infections in the short term, in the long term, the outcome depends on immune robustness. A one-dose strategy may increase the potential for antigenic evolution if immune responses are suboptimal and the virus continues to replicate in some vaccinated people, potentially leading to immune-escape mutations. It is critical to gather serological data from vaccinated people and, to avoid negative outcomes, to ramp up vaccination efforts worldwide. Science, this issue p. 363 A one-dose vaccine policy may increase the potential for viral antigenic evolution in some scenarios. As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues, the deployment of safe and effective vaccines presents a key intervention for mitigating disease severity and spread. Numerous logistical challenges and shortages have emerged alongside the international distribution of approved vaccines. In response, several countries have chosen to delay the second dose in an effort to increase the number of individuals receiving at least one dose. A key question then becomes how the timing of delivery of the second dose will affect future epidemiological and evolutionary outcomes. We build on an existing immuno-epidemiological framework that assumes that, without vaccination, individual immunity after recovery from primary infection may eventually wane, leading to (a potentially reduced) susceptibility to secondary infections. To explore epidemiological outcomes, we extend the model to incorporate two vaccinated classes, corresponding to individuals who have received either one dose or two doses of a SARS-CoV-2 vaccine. As with natural immunity, we allow for one- or two-dose vaccinal immunity to wane, and we consider a continuous spectrum for the interdose period between vaccines. To reflect the increase in available doses resulting from a delayed second dose, we model the rate of administration of the first dose as an increasing function of the interdose period. We then consider evolutionary outcomes by coupling this framework to a simple phylodynamic model for potential viral adaptation under different evolutionary scenarios, each with its own assumptions regarding viral abundance and within-host selection for the different partially susceptible classes. We find that delaying second vaccine doses reduces COVID-19 infections in the short term by increasing the proportion of immune individuals. In the longer term, however, both the infection burden and the relative potential for viral adaptation are highly dependent on the robustness of natural or vaccinal immune responses. Notably, we find that even if immunity conferred by a single vaccine dose is poor, starting with a one-dose policy early on to increase the number of individuals immunized and then switching to the manufacturer-recommended two-dose regime as vaccine capacity increases can mitigate potential negative longer-term epidemiological and evolutionary outcomes. This mitigation can also be achieved by ramping up overall vaccination rates as availability improves. The deployment of SARS-CoV-2 vaccines will strongly shape postpandemic epidemiological trajectories and characteristics of accumulated population immunity. Our models show that the combination of different vaccine dosing regimes and variations in the robustness of natural and vaccinal immunity may result in a wide range of potential epidemiological and evolutionary outcomes in the medium term. It is therefore imperative to determine the strength and duration of clinical protection and transmission-blocking immunity through careful clinical evaluations in order to enforce sound public policies. In places where vaccine deployment is delayed and vaccination rates are low, our results stress the subsequent negative epidemiological and evolutionary impacts that may emerge. Particularly because these consequences (for example, the evolution of new variants) could emerge as global problems, there is an urgent need for global equity in vaccine distribution and deployment. An immuno-epidemiological model (left) coupled with a phylodynamic model (middle) is used to explore projections for COVID-19 infection burden and immune landscapes (top right) and potential rates of SARS-CoV-2 viral adaptation (bottom right) in the medium term. The accompanying online interactive application (http://grenfelllab.princeton.edu/sarscov2vaccine) can be used to explore these projections for a broad range of model parameters. Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.