Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes

doi:10.1126/science.abg8663

GSTDTAP > 气候变化

DOI	10.1126/science.abg8663
	Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes
	Chadi M. Saad-Roy; Sinead E. Morris; C. Jessica E. Metcalf; Michael J. Mina; Rachel E. Baker; Jeremy Farrar; Edward C. Holmes; Oliver G. Pybus; Andrea L. Graham; Simon A. Levin; Bryan T. Grenfell; Caroline E. Wagner
	2021-04-23
发表期刊	Science
出版年	2021
英文摘要	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][1] ### INTRODUCTION 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. ### RATIONALE 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. ### RESULTS 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. ### CONCLUSION 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. ![Figure][2] The relative robustness of one- or two-dose vaccinal immunity and natural immunity shape future epidemiological and evolutionary outcomes for SARS-CoV-2. 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 () 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. [1]: /lookup/doi/10.1126/science.abg8663 [2]: pending:yes
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条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/324075
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推荐引用方式 GB/T 7714	Chadi M. Saad-Roy,Sinead E. Morris,C. Jessica E. Metcalf,et al. Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes[J]. Science,2021.
APA	Chadi M. Saad-Roy.,Sinead E. Morris.,C. Jessica E. Metcalf.,Michael J. Mina.,Rachel E. Baker.,...&Caroline E. Wagner.(2021).Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.Science.
MLA	Chadi M. Saad-Roy,et al."Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes".Science (2021).