Could less be more? Accounting for fractional-dose regimens and different number of vaccine doses when measuring the impact of the RTS, S/AS01E malaria vaccine

Nelli Westercamp; Lawrence Osei-Tutu; Lode Schuerman; Simon K Kariuki; Anne Bollaerts; Cynthia K Lee; Aaron M Samuels; Christian Ockenhouse; Dennis K Bii; Samuel Adjei; Martina Oneko; Marc Lievens; Maame Anima Attobrah Sarfo; Cecilia Atieno; Ashura Bakari; Tony Sang; Maame Fremah Kotoh-Mortty; Kephas Otieno; François Roman; Patrick Boakye Yiadom Buabeng; Yaw Ntiamoah; Daniel Ansong; Tsiri Agbenyega; Opokua Ofori-Anyinam

doi:10.1093/infdis/jiae075

Could less be more? Accounting for fractional-dose regimens and different number of vaccine doses when measuring the impact of the RTS, S/AS01E malaria vaccine

J Infect Dis. 2024 Mar 4:jiae075. doi: 10.1093/infdis/jiae075. Online ahead of print.

Authors

Nelli Westercamp¹, Lawrence Osei-Tutu², Lode Schuerman³, Simon K Kariuki⁴, Anne Bollaerts³, Cynthia K Lee⁵, Aaron M Samuels^{1

6}, Christian Ockenhouse⁵, Dennis K Bii⁴, Samuel Adjei², Martina Oneko⁴, Marc Lievens³, Maame Anima Attobrah Sarfo², Cecilia Atieno⁴, Ashura Bakari², Tony Sang⁴, Maame Fremah Kotoh-Mortty², Kephas Otieno⁴, François Roman³, Patrick Boakye Yiadom Buabeng², Yaw Ntiamoah², Daniel Ansong², Tsiri Agbenyega², Opokua Ofori-Anyinam³

Affiliations

¹ Malaria Branch, Division of Parasitic Diseases and Malaria, Global Health Center, Centers for Disease Control and Prevention, Atlanta, GA30333, US.
² Kwame Nkrumah University of Science and Technology/Agogo Presbyterian Hospital, Agogo, Asante Akyem, Ghana.
³ GSK, Wavre 1300, Belgium.
⁴ Centre for Global Health Research, Kenya Medical Research Institute, 40100, Kisumu, Kenya.
⁵ PATH's Malaria Vaccine Initiative, Washington, DC 20001, US.
⁶ Malaria Branch, Division of Parasitic Diseases and Malaria, Global Health Center, Centers for Disease Control and Prevention, 40100, Kisumu, Kenya.

PMID: 38438123
DOI: 10.1093/infdis/jiae075

Abstract

Background: The RTS, S/AS01E malaria vaccine (RTS, S) is recommended for children in moderate-to-high Plasmodium falciparum malaria transmission areas. This phase 2b trial (NCT03276962) evaluates RTS, S fractional- and full-dose regimens in Ghana and Kenya.

Methods: 1500 children aged 5-17 months were randomised (1:1:1:1:1) to receive RTS, S or rabies control vaccine. RTS, S groups received two full RTS, S doses at month (M)0/M1 followed by either full (groups R012-20, R012-14-26) or fractional (1/5) doses (groups Fx012-14-26, Fx017-20-32).

Results: At M32 post-first dose, vaccine efficacy (VE) against clinical malaria (all episodes) ranged from 38% (R012-20; 95%CI: 24-49) to 53% (R012-14-26; 95%CI: 42-62). Vaccine impact estimates (cumulative number of malaria cases averted/1000 children vaccinated) were 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional- versus full-dose), in a post-hoc analysis, we also estimated cases averted/1000 RTS, S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), 880 (Fx017-20-32).

Conclusions: VE against clinical malaria was similar in all RTS, S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If borne out through trial end (M50), these observations underscore the means to reduce cost per regimen with a goal of maximising impact and optimising supply.

Keywords: RTS,S/AS01E; clinical malaria; dose sparing; fractional-dose regimen; malaria vaccine; vaccine efficacy; vaccine impact.