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Identifying and reducing risks of neurological complications associated with vaccination

Nature Reviews Neurology volume 20, pages 541–554 (2024)Cite this article

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Abstract

Vaccines protect against many infectious diseases, including some that can directly or indirectly cause nervous system damage. Serious neurological consequences of immunization are typically extremely rare, although they have the potential to jeopardize vaccination programmes, as demonstrated most recently during the COVID-19 pandemic. Neurologists have an important role in identifying safety signals at population and individual patient levels, as well as providing advice on the benefit–risk profile of vaccination in cohorts of patients with diverse neurological conditions. This article reviews the links between vaccination and neurological disease and considers how emerging signals can be evaluated and their mechanistic basis identified. We review examples of neurotropic infections with live attenuated vaccines, as well as neuroimmunological and neurovascular sequelae of other types of vaccines. We emphasize that such risks are typically dwarfed by neurological complications associated with natural infection and discuss how the risks can be further mitigated. The COVID-19 pandemic has highlighted the need to rapidly identify and minimize neurological risks of vaccination, and we review the structures that need to be developed to protect public health against these risks in the future.

Key points

  • Vaccines have a key public health role in protecting populations against infectious diseases, including neurological diseases caused by infections.

  • Serious neurological complications of vaccination are extremely rare, but when they do occur they have the potential to jeopardize vaccination programmes.

  • Live attenuated vaccines, such as the yellow fever and poliomyelitis vaccines, carry a very small risk of neurotropic infections; vaccine-specific and recipient-specific factors can predispose to these complications.

  • Very rare neurological complications of vaccination include neuroimmunological conditions such as Guillain–Barré syndrome, acute disseminated encephalomyelitis and narcolepsy, and neurovascular conditions such as cerebral venous sinus thrombosis and stroke.

  • Apart from live vaccines in immunosuppressed individuals and the yellow fever vaccine in people with myasthenia gravis, vaccination is typically safe in individuals with neurological disease, with strongly positive benefit–risk profiles.

  • Recent advances in data linkage have allowed monitoring of the neurological safety profile of vaccines as they are rolled out, almost in real time, and have enabled these risks to be weighed against the risks of infection in unvaccinated individuals.

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Fig. 1: Overview of clinical development and safety studies.
Fig. 2: Risk factors for yellow fever vaccine-associated neurotropic disease.
Fig. 3: Revertant neurovirulence of the oral poliovirus vaccine.
Fig. 4: Guillain–Barré syndrome as a neuroimmunological sequela of vaccination.
Fig. 5: Novel neuroimmunological and neurovascular sequelae of COVID-19 vaccination using adenovirus vector approaches.
Fig. 6: Improving vaccine safety.

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Acknowledgements

D.P.J.H. is supported by a Wellcome Trust Senior Research Fellowship (215621/Z/19/Z) and the Medical Research Foundation, and his research is supported by the UK Dementia Research Institute (Medical Research Council). L.H. is supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre, UK. L.T. is supported by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool, UK in partnership with the UK Health Security Agency (UK HSA), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. L.T. is based at the University of Liverpool. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or the UK HSA.

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Authors and Affiliations

  1. Nuffield Department of Neurosciences, Department of Psychiatry, University of Oxford, Oxford, UK

    Lahiru Handunnetthi

  2. Oxford Vaccine Group, University of Oxford, Oxford, UK

    Maheshi N. Ramasamy

  3. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK

    Lance Turtle

  4. UK Dementia Research Institute, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    David P. J. Hunt

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  1. Lahiru Handunnetthi
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  2. Maheshi N. Ramasamy
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  3. Lance Turtle
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  4. David P. J. Hunt
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The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to David P. J. Hunt.

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Competing interests

L.T. has received consulting fees from the UK Medicines and Healthcare products Regulatory Agency (MHRA); consulting fees from AstraZeneca and Synairgen, paid to the University of Liverpool, UK; speakers’ fees from Eisai; and support for conference attendance from AstraZeneca. L.T. was a member of the MHRA yellow fever vaccine safety expert working group. D.P.J.H. is a Commissioner for the UK Government Commission for Human Medicines. L.H. and M.N.R. declare no competing interests.

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Related links

Adverse Events Following Immunization (AEFI): https://www.who.int/publications/m/item/reporting-form-aefi

Vaccine Adverse Event Reporting System (VAERS): https://vaers.hhs.gov/

Vaccine Damage Payment Scheme: https://www.gov.uk/vaccine-damage-payment

Yellow Card: https://yellowcard.mhra.gov.uk/

Glossary

Bayesian analysis

Modelling method that incorporates prior data to infer the probability of a given hypothesis.

Embryonated chicken eggs

Fertilized chicken eggs that have been allowed to develop into embryos over 5–12 days and are used for viral cell culture.

Seed lot system

A manufacturing technique in which batches of vaccine are made using a standardized master cell and/or virus stock.

Time-invariant confounding

A confounder that remains constant across the duration of the study period (for example, sex or ethnicity).

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Handunnetthi, L., Ramasamy, M.N., Turtle, L. et al. Identifying and reducing risks of neurological complications associated with vaccination. Nat Rev Neurol 20, 541–554 (2024). https://doi.org/10.1038/s41582-024-01000-7

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