---
title: "Natural direct effects of vaccines and post-vaccination behaviour: implications for vaccine effect"
id: "pubmed-42424826"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42424826"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42424826/"
doi: "10.1016/j.vaccine.2026.128888"
published_at: "2026-08-30T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Natural direct effects of vaccines and post-vaccination behaviour: implications for vaccine effect
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42424826
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42424826/)
- **DOI:** [10.1016/j.vaccine.2026.128888](https://doi.org/10.1016%2Fj.vaccine.2026.128888)
- **Published At:** 2026-08-30T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The article examines how knowledge of protection from **vaccines** can change vaccinated individuals' behaviour, potentially increasing exposure to pathogens and reducing observed **vaccine effectiveness**. - The authors frame the relevant quantity as the **natural direct effect**: the effect of vaccination on disease if the vaccine's influence on behaviour (the mediator) were blocked. - Estimating natural direct effects in this context is practically challenging; the paper discusses methodological complications rather than providing new empirical estimates. - Key complications include confounding between exposure and outcome and between mediator and outcome driven by **healthcare-seeking behaviour**. - The authors highlight the need to collect data on behaviour and to evaluate whether vaccines induce **riskier behaviour** post-vaccination. - The paper outlines possible approaches to facilitate estimation of these direct effects, emphasizing causal inference concepts such as potential outcomes and direct effects. - The review concludes by stressing the relevance of understanding vaccine effects when behavioural mediation is absent and the importance of integrating behavioural measurement into vaccine effectiveness studies.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 9. # Natural direct effects of vaccines and post-vaccination behaviour [Bronner P Gonçalves](https://pubmed.ncbi.nlm.nih.gov/?term=Gon%C3%A7alves+BP&cauthor_id=42424826)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#full-view-affiliation-1 "University of Surrey, Guildford, United Kingdom; ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: bronnergoncalves@gmail.com."), [Piero L Olliaro](https://pubmed.ncbi.nlm.nih.gov/?term=Olliaro+PL&cauthor_id=42424826)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#full-view-affiliation-2 "ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: piero.olliaro@ndm.ox.ac.uk."), [Sheena G Sullivan](https://pubmed.ncbi.nlm.nih.gov/?term=Sullivan+SG&cauthor_id=42424826)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#full-view-affiliation-3 "School of Clinical Sciences, Monash University, Melbourne, VIC, Australia; Fielding School of Public Health, University of California, Los Angeles \(UCLA\), Los Angeles, CA, United States."), [Benjamin J Cowling](https://pubmed.ncbi.nlm.nih.gov/?term=Cowling+BJ&cauthor_id=42424826)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#full-view-affiliation-4 "WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: bcowling@hku.hk.") Affiliations Expand ### Affiliations * 1 University of Surrey, Guildford, United Kingdom; ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: bronnergoncalves@gmail.com. * 2 ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: piero.olliaro@ndm.ox.ac.uk. * 3 School of Clinical Sciences, Monash University, Melbourne, VIC, Australia; Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, United States. * 4 WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: bcowling@hku.hk. * PMID: **42424826** * DOI: [ 10.1016/j.vaccine.2026.128888 ](https://doi.org/10.1016/j.vaccine.2026.128888) Item in Clipboard Review # Natural direct effects of vaccines and post-vaccination behaviour Bronner P Gonçalves et al. Vaccine. 2026. Show details Display options Display options Format Abstract PubMed PMID Vaccine Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Vaccine%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Vaccine%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42424826/) . 2026 Aug 30:89:128888. doi: 10.1016/j.vaccine.2026.128888. Epub 2026 Jul 9. ### Authors [Bronner P Gonçalves](https://pubmed.ncbi.nlm.nih.gov/?term=Gon%C3%A7alves+BP&cauthor_id=42424826)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#short-view-affiliation-1 "University of Surrey, Guildford, United Kingdom; ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: bronnergoncalves@gmail.com."), [Piero L Olliaro](https://pubmed.ncbi.nlm.nih.gov/?term=Olliaro+PL&cauthor_id=42424826)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#short-view-affiliation-2 "ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: piero.olliaro@ndm.ox.ac.uk."), [Sheena G Sullivan](https://pubmed.ncbi.nlm.nih.gov/?term=Sullivan+SG&cauthor_id=42424826)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#short-view-affiliation-3 "School of Clinical Sciences, Monash University, Melbourne, VIC, Australia; Fielding School of Public Health, University of California, Los Angeles \(UCLA\), Los Angeles, CA, United States."), [Benjamin J Cowling](https://pubmed.ncbi.nlm.nih.gov/?term=Cowling+BJ&cauthor_id=42424826)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42424826/#short-view-affiliation-4 "WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: bcowling@hku.hk.") ### Affiliations * 1 University of Surrey, Guildford, United Kingdom; ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: bronnergoncalves@gmail.com. * 2 ISARIC, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom. Electronic address: piero.olliaro@ndm.ox.ac.uk. * 3 School of Clinical Sciences, Monash University, Melbourne, VIC, Australia; Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, United States. * 4 WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: bcowling@hku.hk. * PMID: **42424826** * DOI: [ 10.1016/j.vaccine.2026.128888 ](https://doi.org/10.1016/j.vaccine.2026.128888) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Knowledge of the protection afforded by vaccines might, in some circumstances, modify a vaccinated individual's behaviour, potentially increasing exposure to pathogens and hindering effectiveness. This possibility is usually left unaddressed in vaccine effectiveness studies. Here, we argue that effects of vaccines on disease when their influence on behaviour is blocked are relevant. This type of effect corresponds, by definition, to natural direct effects. There are, however, practical complications for the estimation of natural direct effects in this context. Here, we discuss some of these issues, including exposure-outcome and mediator-outcome confounding by healthcare seeking behaviour, and possible approaches to facilitate estimates of these effects. This work highlights the importance of data collection on behaviour, of assessing whether vaccines induce "riskier" behaviour, and of understanding the potential effects of vaccines when their influence on behaviour is blocked. **Keywords:** Causal inference; Direct effects; Potential outcomes; Vaccine effectiveness. Copyright © 2026 Elsevier Ltd. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin Cowling and Sheena Sullivan report a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Benjamin Cowling and Sheena Sullivan report a relationship with Fosun Pharma USA Inc that includes: consulting or advisory. Benjamin Cowling and Sheena Sullivan report a relationship with GlaxoSmithKline LLC that includes: consulting or advisory. Benjamin Cowling reports a relationship with Haleon UK Services Limited that includes: consulting or advisory. Benjamin Cowling reports a relationship with Moderna Inc that includes: consulting or advisory. Benjamin Cowling and Sheena Sullivan report a relationship with Novavax Inc that includes: consulting or advisory. Benjamin Cowling reports a relationship with Pfizer Inc that includes: consulting or advisory. Benjamin Cowling reports a relationship with Roche that includes: consulting or advisory. Benjamin Cowling and Sheena Sullivan report a relationship with Sanofi Pasteur Inc that includes: consulting or advisory. Sheena Sullivan reports a relationship with CSL Seqirus Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Personality Theories. ](https://pubmed.ncbi.nlm.nih.gov/42475469/) Gallios JM, Iyer V, Kaylor LE.Gallios JM, et al.2026 Jun 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–.2026 Jun 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–.PMID: 42475469Free Books & Documents. * [ Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study. ](https://pubmed.ncbi.nlm.nih.gov/38367758/) Barros FC, Gunier RB, Rego A, Sentilhes L, Rauch S, Gandino S, Teji JS, Thornton JG, Kachikis AB, Nieto R, Craik R, Cavoretto PI, Winsey A, Roggero P, Rodriguez GB, Savasi V, Kalafat E, Giuliani F, Fabre M, Benski AC, Coronado-Zarco IA, Livio S, Ostrovska A, Maiz N, Castedo Camacho FR, Peterson A, Deruelle P, Giudice C, Casale RA, Salomon LJ, Soto Conti CP, Prefumo F, Mohamed Elbayoumy EZ, Vale M, Hernández V, Chandler K, Risso M, Marler E, Cáceres DM, Crespo GA, Ernawati E, Lipschuetz M, Ariff S, Takahashi K, Vecchiarelli C, Hubka T, Ikenoue S, Tavchioska G, Bako B, Ayede AI, Eskenazi B, Bhutta ZA, Kennedy SH, Papageorghiou AT, Villar J; INTERCOVID-2022 International Consortium.Barros FC, et al.Am J Obstet Gynecol. 2024 Oct;231(4):460.e1-460.e17. doi: 10.1016/j.ajog.2024.02.008. Epub 2024 Feb 16.Am J Obstet Gynecol. 2024.PMID: 38367758 * [ Factors that influence caregivers' and adolescents' views and practices regarding human papillomavirus (HPV) vaccination for adolescents: a qualitative evidence synthesis. ](https://pubmed.ncbi.nlm.nih.gov/40232221/) Cooper S, Schmidt BM, Jama NA, Ryan J, Leon N, Mavundza EJ, Burnett RJ, Tanywe AC, Wiysonge CS.Cooper S, et al.Cochrane Database Syst Rev. 2025 Apr 15;4(4):CD013430. doi: 10.1002/14651858.CD013430.pub2.Cochrane Database Syst Rev. 2025.PMID: 40232221Free PMC article. * [ Healthcare workers' perceptions and experiences of communicating with people over 50 years of age about vaccination: a qualitative evidence synthesis. ](https://pubmed.ncbi.nlm.nih.gov/34282603/) Glenton C, Carlsen B, Lewin S, Wennekes MD, Winje BA, Eilers R; VITAL consortium.Glenton C, et al.Cochrane Database Syst Rev. 2021 Jul 20;7(7):CD013706. doi: 10.1002/14651858.CD013706.pub2.Cochrane Database Syst Rev. 2021.PMID: 34282603Free PMC article. * [ Vaccine effects and impact of vaccination programmes in post-licensure studies. ](https://pubmed.ncbi.nlm.nih.gov/23856332/) Hanquet G, Valenciano M, Simondon F, Moren A.Hanquet G, et al.Vaccine. 2013 Nov 19;31(48):5634-42. doi: 10.1016/j.vaccine.2013.07.006. 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