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

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...

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Published innpj vaccines Vol. 6; no. 1; p. 55
Main Authors Remarque, Edmond J., Faber, Bart W., Rodriguez Garcia, Roberto, Oostermeijer, Herman, Sirima, Sodiomon B., Nebie Ouedraogo, Issa, Kara, Leila, Launay, Odile, Houard, Sophie, Leroy, Odile, Kocken, Clemens H. M.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 14.04.2021
Nature Publishing Group
Nature Research
Nature Portfolio
Subjects
631/250/255/1629
631/250/590/2294
692/699/255/1629
Antibodies
Antigens
Biomedical and Life Sciences
Biomedicine
Blood
Immunization
Immunology
Infectious Diseases
Life Sciences
Malaria
Medical Microbiology
Public Health
Vaccine
Vaccines
Vaccinology
Vector-borne diseases
Virology
Malaria
Protein vaccines
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Summary: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.
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PMCID: PMC8046791
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-021-00319-2