There is a threat that evolutionary responses can render vaccines ineffective, as illustrated by the emergence of the increasingly virulent Marek Disease Virus strains in poultry following vaccination campaigns. Assessing the ‘evolution-proof’ nature of vaccines targeting human viruses is challenging because it requires an understanding of the epidemiology, the within-host ecology and the evolutionary potential of the virus. To date, most investigations into the spread of vaccine-resistant strains are theoretical and are rarely constrained by data.
We propose a novel alliance between evolutionary ecology and clinical research to assess the risk of vaccines selecting for resistant or virulent strains. Human papillomaviruses (HPV) and their vaccines provide an ideal study system. However, the scope of the project is wider and encompasses other DNA viruses. The project is divided into three parts. In Part I, we will decipher HPV within-host dynamics in genital infections. By combining mathematical modelling and longitudinal patient data, we will be able to parameterise within-host models and compare them. In Part II, we will jointly analyse host, virus and genital microbiota diversity using a community ecology approach to understand the infectious process. These results will be integrated into evolutionary epidemiology models allowing for diverse infections. In Part III, we will estimate virus substitution rates and use the results from Parts I and II to develop a multilevel analysis of HPV evolution in response to vaccination. We will also tackle more general questions related to the evolution of the virulence of human oncoviruses.
A major asset of the project is the collection of clinical data in order to address a major public health issue using ideas and methods from evolutionary ecology. This will set a new agenda for the study of human viral infections and establish a perennial leading research group in Europe.
For more details (in French), about the clinical study, see the PAPCLEAR webpage.
Murall CL & 42 others (2019) Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study. BMJ Open 9(6):e025129
Murall C. L., Jackson R., Zehbe I., Boulle N., Segondy M. & Alizon S. (2019) Epithelial stratification shapes infection dynamics. PLoS Comput Biol 15(1):e1006646
Murall C. L. & Alizon S. (2019) Modelling the evolution of viral oncogenesis. Phil Trans R Soc Lond B 374(1773):20180302
Alizon S., Bravo I. G., Farrell P. J. & Roberts S. (2019) Towards a multi-level and a multi-disciplinary approach to DNA oncovirus virulence. Phil Trans R Soc Lond B 374(1773):20190041
Kamiya T., Mideo N. & Alizon S. (2018) Coevolution of virulence and immunosuppression in multiple infections. J Evol Biol 31(7):995-1005
Alizon S. & Méthot P. (2018) Reconciling Pasteur and Darwin to control infectious diseases. PLoS Biol 16(1):e2003815
Alizon S., Murall C. L. & Bravo I. G. (2017) Why Human Papillomavirus Acute Infections Matter. Viruses 9(10):293For further details and PDFs, see our publications »