article published yes Simon Rella author B4765ACA-AA38-11E9-AC9A-0930E6697425 Yuliya A. Kulikova author Aygul Minnegalieva author 87DF77F0-1D9A-11EA-B6AE-CE443DDC885E Fyodor Kondrashov author 44FDEF62-F248-11E8-B48F-1D18A9856A870000-0001-8243-4694 GaTk department Vaccination is the most effective tool to control infectious diseases. However, the evolution of vaccine resistance, exemplified by vaccine resistance in SARS-CoV-2, remains a concern. Here, we model complex vaccination strategies against a pathogen with multiple epitopes—molecules targeted by the vaccine. We found that a vaccine targeting one epitope was ineffective in preventing vaccine escape. Vaccine resistance in highly infectious pathogens was prevented by the full-epitope vaccine, that is, one targeting all available epitopes, but only when the rate of pathogen evolution was low. Strikingly, a bet-hedging strategy of random administration of vaccines targeting different epitopes was the most effective in preventing vaccine resistance in pathogens with the low rate of infection and high rate of evolution. Thus, complex vaccination strategies, when biologically feasible, may be preferable to the currently used single-vaccine approaches for long-term control of disease outbreaks, especially when applied to livestock with near 100% vaccination rates. https://research-explorer.ista.ac.at/download/18307/18453/2024_Evolution_Rella.pdf application/pdfno https://creativecommons.org/licenses/by-nc-nd/4.0/ Oxford University Press2024 eng 1558-5646 38990788 00128658190000110.1093/evolut/qpae106 78101722-1738 https://research-explorer.ista.ac.at/record/14862 https://research-explorer.ista.ac.at/record/20811 https://github.com/Simon-Re/complex-vaccination S. Rella, Y.A. Kulikova, A. Minnegalieva, F. Kondrashov, Evolution: International Journal of Organic Evolution 78 (2024) 1722–1738. Rella S, Kulikova YA, Minnegalieva A, Kondrashov F. 2024. Complex vaccination strategies prevent the emergence of vaccine resistance. Evolution: International journal of organic evolution. 78(10), 1722–1738. S. Rella, Y. A. Kulikova, A. Minnegalieva, and F. Kondrashov, “Complex vaccination strategies prevent the emergence of vaccine resistance,” <i>Evolution: International journal of organic evolution</i>, vol. 78, no. 10. Oxford University Press, pp. 1722–1738, 2024. Rella, Simon, et al. “Complex Vaccination Strategies Prevent the Emergence of Vaccine Resistance.” <i>Evolution: International Journal of Organic Evolution</i>, vol. 78, no. 10, Oxford University Press, 2024, pp. 1722–38, doi:<a href="https://doi.org/10.1093/evolut/qpae106">10.1093/evolut/qpae106</a>. Rella S, Kulikova YA, Minnegalieva A, Kondrashov F. Complex vaccination strategies prevent the emergence of vaccine resistance. <i>Evolution: International journal of organic evolution</i>. 2024;78(10):1722-1738. doi:<a href="https://doi.org/10.1093/evolut/qpae106">10.1093/evolut/qpae106</a> Rella, Simon, Yuliya A. Kulikova, Aygul Minnegalieva, and Fyodor Kondrashov. “Complex Vaccination Strategies Prevent the Emergence of Vaccine Resistance.” <i>Evolution: International Journal of Organic Evolution</i>. Oxford University Press, 2024. <a href="https://doi.org/10.1093/evolut/qpae106">https://doi.org/10.1093/evolut/qpae106</a>. Rella, S., Kulikova, Y. A., Minnegalieva, A., &#38; Kondrashov, F. (2024). Complex vaccination strategies prevent the emergence of vaccine resistance. <i>Evolution: International Journal of Organic Evolution</i>. Oxford University Press. <a href="https://doi.org/10.1093/evolut/qpae106">https://doi.org/10.1093/evolut/qpae106</a> 183072024-10-13T22:01:50Z2026-10-02T10:12:20Z