Passive immunization of Aotus monkeys with human antibodies to the Plasmodium falciparum antigen Pf155/RESA

TY - JOUR

T1 - Passive immunization of Aotus monkeys with human antibodies to the Plasmodium falciparum antigen Pf155/RESA

AU - Berzins, K

AU - Perlmann, H

AU - Wåhlin, B

AU - Ekre, H P

AU - Högh, B

AU - Petersen, E

AU - Wellde, B

AU - Schoenbechler, M

AU - Williams, J

AU - Chulay, J

PY - 1991/4

Y1 - 1991/4

N2 - In order to assess the protective effects of anti-Pf155/RESA antibodies of different specificities in vivo, passive immunizations of Aotus monkeys were performed. Antibodies reactive with the Pf155/RESA repeat sequences (EENV)2 and EENVEHDA were isolated from the immunoglobulin G (IgG) fraction of a pool of plasmas from Liberia by affinity chromatography on synthetic peptides. The two fractions of antibodies differed in specificity but displayed similar capacities to inhibit merozoite invasion in Plasmodium falciparum in vitro cultures. Four groups of monkeys (named groups I to IV) were injected with (i) 160 mg of total control IgG, (ii) 2 mg of IgG affinity purified on (EENV)2, (iii) 2 mg of IgG affinity purified on EENVEHDA, and (iv) 160 mg of total immune IgG, respectively. The monkeys were then challenged with P. falciparum-infected erythrocytes, and the levels of parasitemia and hematocrits as well as other serological parameters were determined daily. Although all groups developed parasitemia, groups II and IV tended to show lower mean daily levels. Three monkeys of group II and two monkeys (each) of groups III and IV self cured the infections, but so did one monkey from the group treated with control IgG (group I). The serum levels of transfused antibodies were low at the peak of parasitemia, suggesting that clearance of parasites was mediated by immune responses mounted by the monkeys. The results indicate that antibodies to epitopes formed by repeats of Pf155/RESA may depress P. falciparum parasitemias and thus that immunogens based on such repeats should be suitable components in a subunit vaccine against asexual stages of P. falciparum.

AB - In order to assess the protective effects of anti-Pf155/RESA antibodies of different specificities in vivo, passive immunizations of Aotus monkeys were performed. Antibodies reactive with the Pf155/RESA repeat sequences (EENV)2 and EENVEHDA were isolated from the immunoglobulin G (IgG) fraction of a pool of plasmas from Liberia by affinity chromatography on synthetic peptides. The two fractions of antibodies differed in specificity but displayed similar capacities to inhibit merozoite invasion in Plasmodium falciparum in vitro cultures. Four groups of monkeys (named groups I to IV) were injected with (i) 160 mg of total control IgG, (ii) 2 mg of IgG affinity purified on (EENV)2, (iii) 2 mg of IgG affinity purified on EENVEHDA, and (iv) 160 mg of total immune IgG, respectively. The monkeys were then challenged with P. falciparum-infected erythrocytes, and the levels of parasitemia and hematocrits as well as other serological parameters were determined daily. Although all groups developed parasitemia, groups II and IV tended to show lower mean daily levels. Three monkeys of group II and two monkeys (each) of groups III and IV self cured the infections, but so did one monkey from the group treated with control IgG (group I). The serum levels of transfused antibodies were low at the peak of parasitemia, suggesting that clearance of parasites was mediated by immune responses mounted by the monkeys. The results indicate that antibodies to epitopes formed by repeats of Pf155/RESA may depress P. falciparum parasitemias and thus that immunogens based on such repeats should be suitable components in a subunit vaccine against asexual stages of P. falciparum.

KW - Adult

KW - Animals

KW - Antibodies, Protozoan/immunology

KW - Antibody Specificity

KW - Antigens, Protozoan/immunology

KW - Aotus trivirgatus

KW - Cross Reactions

KW - Humans

KW - Immunization, Passive

KW - Immunoglobulin G/analysis

KW - Malaria/prevention & control

KW - Plasmodium falciparum/immunology

M3 - Journal article

C2 - 2004828

SN - 0019-9567

VL - 59

SP - 1500

EP - 1506

JO - Infection and Immunity

JF - Infection and Immunity

IS - 4

ER -