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The non-specific and sex-differential effects of vaccines
Open accessAbstract
The textbook view of vaccination is that it functions to induce immune memory of the specific pathogen components of the vaccine, leading to a quantitatively and qualitatively better response if the host is exposed to infection with the same pathogen. However, evidence accumulated over the past few decades increasingly suggests that vaccines can also have non-specific effects on unrelated infections and diseases, with important implications for childhood mortality particularly in low-income settings. Furthermore, many of these non-specific effects, as well as the pathogen-specific effects, of vaccines show differences between the sexes. Here, members of the Optimmunize consortium discuss the evidence for and potential mechanisms of non-specific and sex-differential effects of vaccines, as well as their potential policy implications. Given that the non-specific effects of some vaccines are now being tested for their ability to protect against COVID-19, the authors also comment on the broader implications of these trials.
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“Besides its specific effects, the vaccine has immunity benefits against nontargeted pathogens [2], and in particular against respiratory infections caused by RNA viruses like influenza [3].”
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Cites
Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370
Self-citationDefining trained immunity and its role in health and disease
Netea, M. G., Domínguez-Andrés, J., Barreiro, L. B., Chavakis, T., Divangahi, M., Fuchs, E., Joosten, L. A. B., van der Meer, J. W. M., Mhlanga, M. M., Mulder, W. J. M., et al. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0285-6 · Cited by 2,690
Self-citationCOVID-19: the gendered impacts of the outbreak
Wenham, C., Smith, J., & Morgan, R. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30526-2 · Cited by 1,701
Arts, R. J. W., Moorlag, S. J. C. F. M., Novakovic, B., Li, Y., Wang, S.-Y., Oosting, M., Kumar, V., Xavier, R. J., Wijmenga, C., Joosten, L. A. B., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2017.12.010 · Cited by 1,217
Self-citationThe Xs and Y of immune responses to viral vaccines
Klein, S. L., Jedlicka, A., & Pekosz, A. S. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70049-9 · Cited by 813
Self-citationAssociation of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review
Higgins, J. P. T., Soares‐Weiser, K., López-López, J. A., Κακούρου, Α., Chaplin, K., Christensen, H., Martin, N. K., Sterne, J. A. C., & Reingold, A. L. (2016) · BMJ · doi:10.1136/bmj.i5170 · Cited by 635
A small jab – a big effect: nonspecific immunomodulation by vaccines
Benn, C. S., Netea, M. G., Selin, L. K., & Aaby, P. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.04.004 · Cited by 535
Self-citationCorrelation between universal BCG vaccination policy and reduced mortality for COVID-19Preprint
Miller, A., Reandelar, M. J., Fasciglione, K., Roumenova, V., Li, Y., & Otazu, G. H. (2020) · medRxiv · doi:10.1101/2020.03.24.20042937 · Cited by 520
Sex and Gender Differences in the Outcomes of Vaccination over the Life Course
Flanagan, K. L., Fink, A. L., Plebanski, M., & Klein, S. L. (2017) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060718 · Cited by 508
Self-citationConsidering BCG vaccination to reduce the impact of COVID-19
Curtis, N. C., Sparrow, A., Ghebreyesus, T. A., & Netea, M. G. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31025-4 · Cited by 346
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Bordoni, V., Guarracino, F., Lorusso, A., Merli, P., Ippolito, G., Locatelli, F., & Agrati, C. (2025) · International review of cytology · doi:10.1016/bs.ircmb.2025.03.004 · Cited by 1
Patrick, E., Iuliano, A., Bakare, D., Salako, J., Shittu, F., Bakare, A. A., Uchendu, O. C., Graham, H., McCollum, E. D., Burgess, R. A., et al. (2025) · Vaccine · doi:10.1016/j.vaccine.2025.127211 · Cited by 1
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Holland, C., Oakes, D. B., Sarna, M. K., Chai, K. E. K., Ng, L., & Moore, H. C. (2025) · BMJ Open · doi:10.1136/bmjopen-2025-100476 · Cited by 1
Sevilla, J. P., Burnes, D., & Bloom, D. E. (2026) · Infectious Diseases and Therapy · doi:10.1007/s40121-026-01299-3 · Cited by 1
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Alimdzhanovna, T. G., & Турдиева, Ш. (2026) · Международный журнал научной педиатрии · doi:10.56121/2181-2926-2026-5-1-1205-1212 · Cited by 1
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Oh, J., Lee, K., Yeo, D., Cho, J. K., Kim, T. H., Lee, J. W., Lee, H., Woo, H. G., & Yon, D. K. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71410 · Cited by 1
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Braun, J. (2025) · Current Rheumatology Reports · doi:10.1007/s11926-024-01179-0 · Cited by 1
McNair, D., Hu, H., & Selwyn, C. (2021) · Gates Open Research · doi:10.12688/gatesopenres.13329.1 · Cited by 1
du Toit, L., Gupta, A., Dehbi, H., Darling, T. L., Urusova, D. V., Thirunavukkarasu, S., Boon, A. C. M., Dubberke, E. R., Yun, L., McKinnon, S., et al. (2022) · medRxiv · doi:10.1101/2022.09.09.22279771 · Cited by 1
Trunk, G., Davidović, M., & Bohlius, J. (2022) · medRxiv · doi:10.1101/2022.10.03.22280556 · Cited by 1
Jones, R., & Ponomarenko, A. (2024) · Preprints.org · doi:10.20944/preprints202401.0333.v1
Xie, M., Eyting, M., Bommer, C., Ahmed, H., & Geldsetzer, P. (2024) · medRxiv · doi:10.1101/2024.08.23.24312457 · Cited by 1
Levi, R., Mansuri, F., Jordán, M., & Ladapo, J. A. (2026) · Global Epidemiology · doi:10.1101/2025.04.25.25326460 · Cited by 3
The BCG Vaccine Does not Protect against COVID-19. Evidence from a Natural Experiment in Sweden.Preprint
de Chaisemartin, C. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3621167
de Chaisemartin, C., & de Chaisemartin, L. (2020) · PubMed Central · doi:10.48550/arxiv.2006.05504
King, A. (2020) · EMBO Reports · doi:10.15252/embr.202051496
Enzootische Bronchopneumonie im Kälberbestand – Ansätze zur Problemlösung
Kaske, M. (2020) · veterinär spiegel · doi:10.1055/a-1194-8518
Herweijer, E., Schwamborn, K., Bollaerts, K., Spillmann, A., Cattaert, T., Verstraeten, T., & Hoogstraate, J. A. (2022) · Gastro Hep Advances · doi:10.1016/j.gastha.2022.02.013
Non-specific Effects of Vaccines
Pittet, L. F., Netea, M. G., & Curtis, N. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-79058-1.00003-7
Wang, Y., Giles, M., & Carvalho, N. (2024) · Vaccines · doi:10.3390/vaccines12030232
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Carmi, M., Carmi, E., Assouly, P., Jansac, M.-M. D., Gras, V., Fraitag, S., Marolleau, J., & Reygagne, P. (2025) · Annales de Dermatologie et de Vénéréologie - FMC · doi:10.1016/j.fander.2025.04.006
Asafo‐Agyei, S. B., Ameyaw, E., Nguah, S. B., Paintsil, V., & Ocran, A. A. (2025) · BMC Pediatrics · doi:10.1186/s12887-025-06365-2
Moor, J., Toepfner, N., von Meißner, W., Berner, R., Moor, M. B., Kublickiene, K., Strumann, C., & Chao, C.-M. (2024) · Figshare · doi:10.6084/m9.figshare.27116047
Additional file 1 of Alzheimer’s disease-related transcriptional sex differences in myeloid cells
Coales, I., Tsartsalis, S., Fancy, N. N., Weinert, M., Clode, D., Owen, D., & Matthews, P. (2022) · Figshare · doi:10.6084/m9.figshare.21285653
Moor, J., Toepfner, N., von Meißner, W., Berner, R., Moor, M. B., Kublickiene, K., Strumann, C., & Chao, C.-M. (2024) · Figshare · doi:10.6084/m9.figshare.27116044
Israel, A., Green, I., Ashkenazi, S., Merzon, E., Golan‐Cohen, A., Vinker, S., Magen, E., & Berkun, Y. (2026) · medRxiv · doi:10.64898/2026.01.04.26343402
Protective effect of adult vaccination on the development of dementias: A systematic review
Mariscal-López, E., Agredano-Sanchez, M., López-Gigosos, R. M., Mariscal, A., Fariñas-Guerrero, F., Gutiérrez‐Bedmar, M., & Guts-Chornoknyzha, M. (2026) · Neurología (English Edition) · doi:10.1016/j.nrleng.2026.501939
Cheng, X., Huang, S., Hu, Z., & Fan, X. (2026) · Vaccines · doi:10.3390/vaccines14040300
Remodeling of innate antiviral immunity in aging
Zhang, X., & Yang, Q. (2026) · Cell Insight · doi:10.1016/j.cellin.2026.100362
Yanhong, L. Y. U., Zhang, F., & Zhao, Q. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1950422
Pacheco, M., Aguiar, P. M. V., Ferrinho, P. D. L. G. M., & Fronteira, I. (2026) · JMIR Public Health and Surveillance · doi:10.2196/103278
Stevens, N. E., Botten, R. J., Geake, J. B., Eden, G. L., Lo, W. K., Inauen, J., Solujic, J., Sawka, A., Yelland, L. N., Reid, E. W., et al. (2026) · BMJ Open · doi:10.1136/bmjopen-2026-126924
Self-citationPacheco, M., Aguiar, P. M. V., Ferrinho, P. D. L. G. M., & Fronteira, I. (2026) · doi:10.2196/preprints.103278
Metadata
- Authors
- Aaby, P., Benn, C. S., Flanagan, K. L., Klein, S. L., Kollmann, T. R., Lynn, D. J., & Shann, F.
- Affiliations
- Bandim Health Project (GW)
- University of Southern Denmark (DK)
- University of Tasmania (AU)
- Johns Hopkins University (US)
- The Kids Research Institute Australia (AU)
- Flinders University (AU)
- The University of Melbourne (AU)
- Corresponding author
- Aaby, Peter
- Benn, Christine Stabell
- Flanagan, Katie L.
- Klein, Sabra L.
- Kollmann, Tobias R.
- Lynn, David J.
- Shann, Frank
- ORCID
- Venue
- Nature Reviews Immunology
- Published
- 2020-05-27
- Volume
- 20
- Issue
- 8
- Pages
- 464-470
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC7252419
- OpenAlex
- W3032007913
- Cited by
- 142
- References
- 51
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 24 · 2023: 19 · 2022: 24 · 2021: 25 · 2020: 15
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Bill and Melinda Gates Foundation
- Wellcome Trust
- Children's Hospital Foundation (U19AI118608-02)
- Royal Children's Hospital Foundation
- Government of South Australia
- Australian Government
- Minderoo Foundation
- Flinders Foundation
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Allergy and Infectious Diseases (U19AI118608)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- non-specific vaccine effects, sex differences in immune response, measles vaccine, non-specific immunity, child mortality, low-income settings, COVID-19 pandemic, vaccination policy, immunomodulation, sex differences in immunity, vitamin A supplementation, vaccine design, systems vaccinology, health surveillance systems, Guinea-Bissau
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Humans, Immunity, Innate, Immunologic Memory, Pneumonia, Viral, Sex Characteristics, Vaccination, Vaccines, Coronavirus Infections, Pandemics
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