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Competing Heterogeneities in Vaccine Effectiveness Estimation

Understanding the waning of vaccine-induced protection is important for both immunology and public health. Population heterogeneities in underlying (pre-vaccination) susceptibility and vaccine response can cause measured vaccine effectiveness (mVE) to change over time, even in the absence of pathoge...

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Autores principales: Nikas, Ariel, Ahmed, Hasan, Zarnitsyna, Veronika I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458793/
https://www.ncbi.nlm.nih.gov/pubmed/37631880
http://dx.doi.org/10.3390/vaccines11081312
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author Nikas, Ariel
Ahmed, Hasan
Zarnitsyna, Veronika I.
author_facet Nikas, Ariel
Ahmed, Hasan
Zarnitsyna, Veronika I.
author_sort Nikas, Ariel
collection PubMed
description Understanding the waning of vaccine-induced protection is important for both immunology and public health. Population heterogeneities in underlying (pre-vaccination) susceptibility and vaccine response can cause measured vaccine effectiveness (mVE) to change over time, even in the absence of pathogen evolution and any actual waning of immune responses. We use multi-scale agent-based models parameterized using epidemiological and immunological data, to investigate the effect of these heterogeneities on mVE as measured by the hazard ratio. Based on our previous work, we consider the waning of antibodies according to a power law and link it to protection in two ways: (1) motivated by correlates of risk data and (2) using a within-host model of stochastic viral extinction. The effect of the heterogeneities is given by concise and understandable formulas, one of which is essentially a generalization of Fisher’s fundamental theorem of natural selection to include higher derivatives. Heterogeneity in underlying susceptibility accelerates apparent waning, whereas heterogeneity in vaccine response slows down apparent waning. Our models suggest that heterogeneity in underlying susceptibility is likely to dominate. However, heterogeneity in vaccine response offsets <10% to >100% (median of 29%) of this effect in our simulations. Our study suggests heterogeneity is more likely to ‘bias’ mVE downwards towards the faster waning of immunity but a subtle bias in the opposite direction is also plausible.
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spelling pubmed-104587932023-08-27 Competing Heterogeneities in Vaccine Effectiveness Estimation Nikas, Ariel Ahmed, Hasan Zarnitsyna, Veronika I. Vaccines (Basel) Article Understanding the waning of vaccine-induced protection is important for both immunology and public health. Population heterogeneities in underlying (pre-vaccination) susceptibility and vaccine response can cause measured vaccine effectiveness (mVE) to change over time, even in the absence of pathogen evolution and any actual waning of immune responses. We use multi-scale agent-based models parameterized using epidemiological and immunological data, to investigate the effect of these heterogeneities on mVE as measured by the hazard ratio. Based on our previous work, we consider the waning of antibodies according to a power law and link it to protection in two ways: (1) motivated by correlates of risk data and (2) using a within-host model of stochastic viral extinction. The effect of the heterogeneities is given by concise and understandable formulas, one of which is essentially a generalization of Fisher’s fundamental theorem of natural selection to include higher derivatives. Heterogeneity in underlying susceptibility accelerates apparent waning, whereas heterogeneity in vaccine response slows down apparent waning. Our models suggest that heterogeneity in underlying susceptibility is likely to dominate. However, heterogeneity in vaccine response offsets <10% to >100% (median of 29%) of this effect in our simulations. Our study suggests heterogeneity is more likely to ‘bias’ mVE downwards towards the faster waning of immunity but a subtle bias in the opposite direction is also plausible. MDPI 2023-08-01 /pmc/articles/PMC10458793/ /pubmed/37631880 http://dx.doi.org/10.3390/vaccines11081312 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nikas, Ariel
Ahmed, Hasan
Zarnitsyna, Veronika I.
Competing Heterogeneities in Vaccine Effectiveness Estimation
title Competing Heterogeneities in Vaccine Effectiveness Estimation
title_full Competing Heterogeneities in Vaccine Effectiveness Estimation
title_fullStr Competing Heterogeneities in Vaccine Effectiveness Estimation
title_full_unstemmed Competing Heterogeneities in Vaccine Effectiveness Estimation
title_short Competing Heterogeneities in Vaccine Effectiveness Estimation
title_sort competing heterogeneities in vaccine effectiveness estimation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458793/
https://www.ncbi.nlm.nih.gov/pubmed/37631880
http://dx.doi.org/10.3390/vaccines11081312
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