Accelerated phase Ia/b evaluation of the malaria vaccine candidate PfAMA1 DiCo demonstrates broadening of humoral immune responses

Edmond J Remarque,Herman Oostermeijer,Issa Nebie Ouedraogo,Roberto Rodriguez Garcia,Bart W Faber,Sodiomon B Sirima,Sophie Houard,Odile Leroy,Leila Kara,Clemens H M Kocken,Odile Launay

doi:10.1038/s41541-021-00319-2

Abstract

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. PfAMA1’s polymorphic nature impacts vaccine-induced protection. To address polymorphism, three Diversity Covering (DiCo) protein sequences were designed and tested in a staggered phase Ia/b trial. A cohort of malaria-naive adults received PfAMA1-DiCo adjuvanted with Alhydrogel® or GLA-SE and a cohort of malaria-exposed adults received placebo or GLA-SE adjuvanted PfAMA1 DiCo at weeks 0, 4 and 26. IgG and GIA levels measured 4 weeks after the third vaccination are similar in malaria-naive volunteers and placebo-immunised malaria-exposed adults, and have a similar breadth. Vaccination of malaria-exposed adults results in significant antibody level increases to the DiCo variants, but not to naturally occurring PfAMA1 variants. Moreover, GIA levels do not increase following vaccination. Future research will need to focus on stronger adjuvants and/or adapted vaccination regimens, to induce potentially protective responses in the target group of the vaccine.

Highlights

Intensive efforts have led to a reduction of the malaria burden
One of these blood-stage candidates is the ectodomain of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1)[3,4]
IgG level rises tended to be higher for the 3 Diversity Covering (DiCo) vaccine variants in the GLA-SE as compared to the Alhydrogel® group (p = 0.17, linear mixed models (LMM)), while by contrast rises for the 4 natural variants did not differ for the treatment groups (0.98-fold (0.29 to 3.3), p = 0.98, LMM)

Summary

Introduction

Intensive efforts have led to a reduction of the malaria burden. it remains a major cause of morbidity and mortality, especially in children in sub-Saharan Africa. A strategy to improve malaria vaccine efficacy would be the inclusion of additional blood-stage antigens, of which a number are currently in clinical development (e.g., Rh5, CyRPA, RIPR, MSP3, GLURP, SERA5, EBA & AMA1)[2]. One of these blood-stage candidates is the ectodomain of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1)[3,4]. AMA1 plays an essential role in the red blood cell invasion cascade[3,5,6,7] and anti-AMA1 IgG inhibits red blood cell invasion[8,9]. It is expressed on sporozoites and may confer protection against hepatocyte invasion[10]

Objectives

Methods

Results

Conclusion