Abstract
Vaccination is one of medicine’s greatest achievements; however, its full potential is hampered by considerable variation in efficacy across populations and geographical regions. For example, attenuated malaria vaccines in high-income countries confer almost 100% protection, whereas in low-income regions these same vaccines achieve only 20–50% protection. This trend is also observed for other vaccines, such as bacillus Calmette–Guérin (BCG), rotavirus and yellow fever vaccines, in terms of either immunogenicity or efficacy. Multiple environmental factors affect vaccine responses, including pathogen exposure, microbiota composition and dietary nutrients. However, there has been variable success with interventions that target these individual factors, highlighting the need for a better understanding of their downstream immunological mechanisms to develop new ways of modulating vaccine responses. Here, we review the immunological factors that underlie geographical variation in vaccine responses. Through the identification of causal pathways that link environmental influences to vaccine responsiveness, it might become possible to devise modulatory compounds that can complement vaccines for better outcomes in regions where they are needed most.
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Acknowledgements
This work was supported by grants from the Dutch Research Organization (NWO) (Spinoza prize awarded to M.Y.), the European Research Council (ERC) (ERC advanced grant REVERSE awarded to M.Y.), National Institute of Health Grant (awarded to M.Y. and B.E.), Leiden University Medical Center (LUMC) (Excellent student PhD fellowship awarded to M.M.A.R.v.D.) and LUMC Global (PhD fellowship awarded to J.J.P.).
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M.M.A.R.v.D., J.J.P. and M.Y. researched the data for the article and contributed to the writing of the manuscript. G.N., V.I.K., B.E., H.H.S., P.C.W.H., S.P.J., A.M.E. and L.J.W. contributed to the writing of the manuscript and M.Y., S.P.J. and B.E. finalized the manuscript. All authors reviewed and edited the manuscript before submission.
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Nature Reviews Immunology thanks Bali Pulendran and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Glossary
- Plasmodium falciparum sporozoite (PfSPZ) vaccine
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An experimental vaccine against malaria based on radiation-attenuated whole sporozoites of P. falciparum malaria parasite.
- PfSPZ–chemoprophylaxis attenuated vaccine
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(PfSPZ–CVac). An experimental vaccine against malaria Plasmodium falciparum sporozoites (PfSPZ) based on chemically attenuated whole sporozoites, by co-administering the whole sporozoites of P. falciparum together with an anti-malaria drug, often chloroquine.
- RTS,S malaria subunit vaccine
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A subunit vaccine against malaria adjuvanted with AS01, which is currently the only licensed malaria vaccine.
- Seroconversion
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Achievement of a quantifiable antibody level after vaccination, which is expected to correlate with protection.
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van Dorst, M.M.A.R., Pyuza, J.J., Nkurunungi, G. et al. Immunological factors linked to geographical variation in vaccine responses. Nat Rev Immunol 24, 250–263 (2024). https://doi.org/10.1038/s41577-023-00941-2
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DOI: https://doi.org/10.1038/s41577-023-00941-2
