Feasibility, safety, and impact of the RTS,S/AS01E malaria vaccine when implemented through national immunisation programmes: evaluation of cluster-randomised introduction of the vaccine in Ghana, Kenya, and Malawi

Asante, Kwaku Poku; Mathanga, Don P; Milligan, Paul; Akech, Samuel; Oduro, Abraham; Mwapasa, Victor; Moore, Kerryn A; Kwambai, Titus K; Hamel, Mary J; Gyan, Thomas; Westercamp, Nelli; Kapito-Tembo, Atupele; Njuguna, Patricia; Ansong, Daniel; Kariuki, Simon; Mvalo, Tisungane; Snell, Paul; Schellenberg, David; Welega, Paul; Otieno, Lucas; Chimala, Alfred; Afari, Edwin A; Bejon, Philip; Maleta, Kenneth; Agbenyega, Tsiri; Snow, Robert W; Zulu, Madaliso; Chinkhumba, Jobiba; Samuels, Aaron M; Abubakari, Sulemana Watara; Akumani, Albert; Adu-Gyasi, Dennis; Sarfo, Augustine; Odei-Lartey, Elezier; Agbokey, Francis; Amenga-Etego, Seeba; Gyaase, Stephany; Buabeng, Patrick; Awini, Elizabeth; Sylverken, Justice; Kampim, Aaron; Koram, Kwadwo A; Hodgson, Abraham; Binka, Fred Newton; Okine, Rafiq Nii Attoh; Tweneboah, Peter Ofori; Ondiegi, Bella; Seda, Brian; Akach, Dorcas; Orwa, Gordon; Nyang’au, Isabella; Odunga, Oscar; Gumba, Francis; Copeland, Nathanial; Khazenzi, Cynthia; Mumo, Eda; Musa, Monica; Ogero, Morris; English, Mike; Haji, Adam; Njoroge, Josephine; Msuku, Harrison; Samuel, Vincent; Mariko, Hillary Topazian; Juliano, Jon; Msumba, Lusungu; Mungwira, Randy George; Zimba, Boston Edward; Desai, Meghna; Furrer, Eliane; Aponte, John; Alonso, Pedro; Kalu, Akpaka A; Sillah, Jackson Sophianu

doi:10.1016/s0140-6736(24)00004-7

Cited by 10 publications

(2 citation statements)

References 8 publications

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“…The RTS,S vaccine included 19 NANP repeats and the C-terminal region III-TSR fused to an hepatitis antigen to increase its immunogenicity. Most recently, a modified R21 vaccine has improved protection levels to < 80% [34][35][36] . RTS,S and R21 are now the only malaria vaccines recommended by the World Health Organization (WHO) for prevention of P. falciparum malaria in children 37 .…”

Section: What Considerations Were Made?mentioning

confidence: 99%

Tailoring evolved-ligands to Plasmodium circumsporozoite-protein

coll

2024

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To prevent malaria deathly infections, the Plasmodium circumsporozoite major protein (CSP) have been targeted world-wide to develop most recent vaccines inducing anti-CSP antibodies. In contrast, drug-like anti-CSP to complement that anti-CSP tool-box, remain underdeveloped. Despite the tridimensional coat of disordered-repeats, computational predictions mimicking natural co-evolution tailored evolved ligands to adapt to most ordered CSP cavities. Tens of thousands of parent-generated raw-candidates selected hundreds of fitted-children conformers predicting low nanoMolar affinities, low toxicities, and cross-docking N-terminal signal peptide with C-terminal α-helices or docking C-terminal cavities. These repeat-independent drug-like predictions, could provide some proof-of-concept examples for basic in vitro experimentation

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Section: What Considerations Were Made?mentioning

confidence: 99%

Tailoring evolved-ligands to Plasmodium circumsporozoite-protein

coll

2024

Preprint

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“…In Ghana, the vaccine is administered to children in four doses, beginning at six months, followed by doses at 7, 9, and 18 months [29] . Following the 215,900 doses of malaria vaccine acquired in January 2024, Benin is planning to begin administering three dose malaria vaccine to children at 6, 7, 9, and a 4 th dose as a booster for children under 24 months of age [11].…”

Section: • Description Of the Modelmentioning

confidence: 99%

Estimating the impact of the RTS,S/AS01 malaria vaccine in Benin: A mathematical modelling study

Alohoutade,

Hounsell,

Silal

2024

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BackgroundMalaria constitutes a major public health burden in sub-Saharan Africa. It remains the primary health concern in health care institutions and the leading cause of death in children under five years of age. Since October 2021, the World Health Organization (WHO) has recommended the RTS,S/AS01 malaria vaccine in children in sub-Saharan Africa and other high burden areas wherePlasmodium falciparumtransmission is moderate to high. However, with the exception of Ghana, there is a scarcity of studies modelling the potential impact of the RTS,S/AS01 vaccine in the context of West Africa. This study addresses a gap in research by modelling the additional impact of malaria childhood vaccination onPlasmodium falciparummalaria transmission in Benin.MethodsA compartmental mathematical model has been developed to estimate clinical and severe malaria cases averted in children under the age of five with the primary series (3 doses) of the RTS,S/AS01 malaria vaccine in Benin. Key features of the model include seasonality and the use of insecticide-treated bed nets. Over a period of 10 years, a number of scenarios of vaccine, coverage are simulated. These scenarios included vaccination introduction at different coverage levels to supplement the use of Insecticide-treated bed nets to assess the impact of the RTS,S/AS01 vaccine on malaria transmission in Benin.ResultsThe model projected outcomes in terms of malaria burden alleviation by childhood vaccination in Benin. The combination of malaria childhood vaccination at a coverage equivalent to the national DTP3 and the current uptake of insecticide-treated bed nets is projected to lead to a 45% reduction in malaria cases and deaths among children under five years old in the country from 2025 to 2034. However, a decrease in the use of ITN is projected to lead to an increase in malaria burden, surpassing baseline levels despite vaccine introduction.ConclusionChild vaccination is expected to avert clinical and severe cases of malaria and is an additional tool to advance malaria control efforts in Benin.

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