Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens

TY - JOUR

T1 - Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens

AU - Nielsen, Morten A

AU - Vestergaard, Lasse S

AU - Lusingu, John

AU - Kurtzhals, Jørgen

AU - Giha, Haider A

AU - Grevstad, Berit

AU - Goka, Bamenla Q

AU - Lemnge, Martha M

AU - Jensen, James B

AU - Akanmori, Bartholomew D

AU - Theander, Thor G

AU - Staalsoe, Trine

AU - Hviid, Lars

N1 - Keywords: Africa, Eastern; Animals; Antibodies, Protozoan; Antibody Specificity; Antigens, Protozoan; Antigens, Surface; Child; Child, Preschool; Ghana; Humans; Immunoglobulin G; Indonesia; Malaria, Falciparum; Plasmodium falciparum

PY - 2004

Y1 - 2004

N2 - The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

AB - The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

U2 - 10.1128/IAI.72.6.3531-3535.2004

DO - 10.1128/IAI.72.6.3531-3535.2004

M3 - Journal article

C2 - 15155661

SN - 0019-9567

VL - 72

SP - 3531

EP - 3535

JO - Infection and Immunity

JF - Infection and Immunity

IS - 6

ER -