TY - JOUR

T1 - Plasmodium falciparum AMA1 and CSP antigen diversity in parasite isolates from southern Ghana

AU - Kusi, Kwadwo A

AU - Amoah, Linda E

AU - Acquah, Festus Kojo

AU - Ennuson, Nana Aba

AU - Frempong, Abena F

AU - Ofori, Ebenezer A

AU - Akyea-Mensah, Kwadwo

AU - Kyei-Baafour, Eric

AU - Osei, Frank

AU - Frimpong, Augustina

AU - Singh, Susheel K

AU - Theisen, Michael

AU - Remarque, Edmond J

AU - Faber, Bart W

AU - Belmonte, Maria

AU - Ganeshan, Harini

AU - Huang, Jun

AU - Villasante, Eileen

AU - Sedegah, Martha

N1 - Copyright © 2024 Kusi, Amoah, Acquah, Ennuson, Frempong, Ofori, Akyea-Mensah, Kyei-Baafour, Osei, Frimpong, Singh, Theisen, Remarque, Faber, Belmonte, Ganeshan, Huang, Villasante and Sedegah.

PY - 2024

Y1 - 2024

N2 - INTRODUCTION: Diversity in malarial antigens is an immune evasion mechanism that gives malaria parasites an edge over the host. Immune responses against one variant of a polymorphic antigen are usually not fully effective against other variants due to altered epitopes. This study aimed to evaluate diversity in the Plasmodium falciparum antigens apical membrane antigen 1 (PfAMA1) and circumsporozoite protein (PfCSP) from circulating parasites in a malaria-endemic community in southern Ghana and to determine the effects of polymorphisms on antibody response specificity.METHODS: The study involved 300 subjects, whose P. falciparum infection status was determined by microscopy and PCR. Diversity within the two antigens was evaluated by msp2 gene typing and molecular gene sequencing, while the host plasma levels of antibodies against PfAMA1, PfCSP, and two synthetic 24mer peptides from the conserved central repeat region of PfCSP, were measured by ELISA.RESULTS: Of the 300 subjects, 171 (57%) had P. falciparum infection, with 165 of the 171 (96.5%) being positive for either or both of the msp2 allelic families. Gene sequencing of DNA from 55 clonally infected samples identified a total of 56 non-synonymous single nucleotide polymorphisms (SNPs) for the Pfama1 gene and these resulted in 44 polymorphic positions, including two novel positions (363 and 365). Sequencing of the Pfcsp gene from 69 clonal DNA samples identified 50 non-synonymous SNPs that resulted in 42 polymorphic positions, with half (21) of these polymorphic positions being novel. Of the measured antibodies, only anti-PfCSP antibodies varied considerably between PCR parasite-positive and parasite-negative persons.DISCUSSION: These data confirm the presence of a considerable amount of unique, previously unreported amino acid changes, especially within PfCSP. Drivers for this diversity in the Pfcsp gene do not immediately seem apparent, as immune pressure will be expected to drive a similar level of diversity in the Pfama1 gene.

AB - INTRODUCTION: Diversity in malarial antigens is an immune evasion mechanism that gives malaria parasites an edge over the host. Immune responses against one variant of a polymorphic antigen are usually not fully effective against other variants due to altered epitopes. This study aimed to evaluate diversity in the Plasmodium falciparum antigens apical membrane antigen 1 (PfAMA1) and circumsporozoite protein (PfCSP) from circulating parasites in a malaria-endemic community in southern Ghana and to determine the effects of polymorphisms on antibody response specificity.METHODS: The study involved 300 subjects, whose P. falciparum infection status was determined by microscopy and PCR. Diversity within the two antigens was evaluated by msp2 gene typing and molecular gene sequencing, while the host plasma levels of antibodies against PfAMA1, PfCSP, and two synthetic 24mer peptides from the conserved central repeat region of PfCSP, were measured by ELISA.RESULTS: Of the 300 subjects, 171 (57%) had P. falciparum infection, with 165 of the 171 (96.5%) being positive for either or both of the msp2 allelic families. Gene sequencing of DNA from 55 clonally infected samples identified a total of 56 non-synonymous single nucleotide polymorphisms (SNPs) for the Pfama1 gene and these resulted in 44 polymorphic positions, including two novel positions (363 and 365). Sequencing of the Pfcsp gene from 69 clonal DNA samples identified 50 non-synonymous SNPs that resulted in 42 polymorphic positions, with half (21) of these polymorphic positions being novel. Of the measured antibodies, only anti-PfCSP antibodies varied considerably between PCR parasite-positive and parasite-negative persons.DISCUSSION: These data confirm the presence of a considerable amount of unique, previously unreported amino acid changes, especially within PfCSP. Drivers for this diversity in the Pfcsp gene do not immediately seem apparent, as immune pressure will be expected to drive a similar level of diversity in the Pfama1 gene.

KW - Plasmodium falciparum/genetics

KW - Antigens, Protozoan/genetics

KW - Ghana

KW - Humans

KW - Protozoan Proteins/genetics

KW - Malaria, Falciparum/parasitology

KW - Membrane Proteins/genetics

KW - Antibodies, Protozoan/blood

KW - Female

KW - Adult

KW - Male

KW - Adolescent

KW - Young Adult

KW - Child

KW - Genetic Variation

KW - Child, Preschool

KW - Middle Aged

KW - Sequence Analysis, DNA

KW - Enzyme-Linked Immunosorbent Assay

KW - Polymerase Chain Reaction

KW - Antigenic Variation

KW - DNA, Protozoan/genetics

U2 - 10.3389/fcimb.2024.1375249

DO - 10.3389/fcimb.2024.1375249

M3 - Journal article

C2 - 38808064

VL - 14

JO - Frontiers in Cellular and Infection Microbiology

JF - Frontiers in Cellular and Infection Microbiology

SN - 2235-2988

M1 - 1375249

ER -