In early 2014 the RTS,S malaria vaccine completed Phase III trials in 11 trial sites throughout sub-Saharan Africa. In October 2021, the WHO recommended the vaccine for wider roll-out in malaria endemic areas of sub-Saharan Africa. We have been involved in modelling work to better understand the mode of action of the vaccine and to use these insights to estimate the cost-effectiveness and public health impact of the vaccine.
Starting with pooled data from the Phase II studies we developed models to identify the relationship between anti-CSP antibodies and protection against infection, and to estimate how immunity against infection and clinical disease wanes over time in different transmission settings. Upon completion of the Phase III trial, we refitted this model with the more informative individual-level data, and used the fitted model to estimate the number of cases and deaths averted if the vaccine were to be rolled out under a variety of delivery regimens. Throughout this process we worked closely with the WHO and three other major modelling groups (GSK Vaccines, the Institute for Disease Modeling, and the Swiss Tropical and Public Health Institute) as part of a rigorous harmonisation and model comparison exercise. Our conclusions were presented to the WHO Strategic Advisory Group of Experts (SAGE) and Malaria Policy Advisory Committee (MPAC), and formed one of many lines of evidence considered by the WHO prior to a recommendation decision.
In more recent work we have focussed on incorporating data from studies of different RTS,S dosing regimens to understand the relative roles of antibody titre and avidity, and on formulating target product profiles to inform development of second-generation vaccines. We also use population-level models to identify optimal strategies for the rollout of RTS,S vaccination, in the context of limited supply, and the relative impact of RTS,S compared with (and in combination with) other interventions.
We continue to work closely with the WHO and PATH to inform policy decisions about the most efficient use of the RTS,S vaccine.
Unwin H, Mwandigha L, Winskill P, Ghani A, Hogan Aet al., 2021, Analysis of the potential for a malaria vaccine to reduce gaps in malaria intervention coverage, Malaria Journal, Vol: 20, Pages: 1-11, ISSN: 1475-2875
Hogan AB, Winskill P, Ghani AC (2020) Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa: a modelling study, PLoS Medicine, DOI: 10.1371/journal.pmed.1003377.
Thompson HA, Hogan AB, Walker PGT, White MT, Cunnington AJ, Ockenhouse CF, Ghani AC (2020) Modelling the roles of antibody titre and avidity in protection from Plasmodium falciparum malaria infection following RTS,S/AS01 vaccination. Vaccine. DOI: 10.1016/j.vaccine.2020.09.069.
Hogan AB, Winskill P, Verity R, Griffin JT, Ghani AC (2018) Modelling population-level impact to inform target product profiles for childhood malaria vaccines. BMC Medicine. 16:1–11. DOI: 10.1186/s12916-018-1095-6
Penny, MA, Verity, R, Bever, CA, Sauboin, C, Galactionova, K, Flasche, S, White, MT, Wenger, EA, Van de Velde, N, Pemberton-Ross, P, Griffin, JT, Smith, TA, Eckhoff, PA, Muhib, F, Jit, M, Ghani, AC. (2015). Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models. The Lancet, Epub ahead of print. Publisher’s link.
White, MT, Verity, R, Griffin, JT, Asante, KP, Owusu-Agyei, S, Greenwood, B, Drakeley, C, Gesase, S, Lusingu, J, Ansong, D, Adjei, S, Agbenyega, T, Ogutu, B, Otieno, L, Otieno, W, Agnandji, ST, Lell, B, Kremsner, P, Hoffman, I, Martinson, F, Kamthunzu, P, Tinto, H, Valea, I, Sorgho, H, Oneko, M, Otieno, K, Hamel, MJ, Salim, N, Mtoro, A, Abdulla, S, Aide, P, Sacarlal, J, Aponte, JJ, Njuguna, P, Marsh, K, Bejon, P, Riley, EM, Ghani, AC, (2015). Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial, Lancet Infectious Diseases, 15. Publisher’s link.
Winskill, P, Walker, PGT, Griffin, JT, Ghani, AC,(2017),Modelling the cost-effectiveness of introducing the RTS,S malaria vaccine relative to scaling up other malaria interventions in sub-Saharan Africa, BMJ Global Health, 2(1), e000090. Publisher's link.