Induction of cytolytic and antibody responses using Plasmodium falciparum repeatless circumsporozoite protein encapsulated in liposomes.
Plasmodium circumsporozoite (CS) protein-induced antibody and T-cell responses are considered to be important in protective immunity. Since the key repeat determinant of the CS protein may actually restrict the recognition of other potential T- and B-cell sites, a modified Plasmodium falciparum CS protein lacking the central repeat region, RLF, was expressed in Escherichia coli. On purification, RLF was encapsulated into liposomes [L(RLF)] and used for the in vivo induction of cytolytic T lymphocytes (CTL) and antibodies. Immunization of B10.Br (H-2k) mice with L(RLF), but not with RLF, induced CD8+ CTL specific for the P. falciparum CS protein CTL epitope, amino acid residues 368-390. Anti-L(RLF) serum reacted with antigens on intact sporozoites and inhibited sporozoite invasion of hepatoma cells. Antibody specificity studies in New Zealand White rabbits revealed new B-cell sites localized in amino acid residues 84-94, 91-99, 97-106 and 367-375. Although the mechanisms by which liposomes enhance cellular and humoral immune responses remain unknown, liposome-formulated vaccines have been well tolerated in humans; hence, their use in vaccines, when efficacy depends on antibody and CTL responses, may be broadly applicable.
White
K
K
Department of Immunology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Krzych
U
U
Gordon
D M
DM
Porter
T G
TG
Richards
R L
RL
Alving
C R
CR
Deal
C D
CD
Hollingdale
M
M
Silverman
C
C
Sylvester
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001483:Base Sequence; D016827:CD8 Antigens / Q000276:immunology; D004337:Drug Carriers; D000939:Epitopes / Q000276:immunology; D005260:Female; D007114:Immunization; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D011817:Rabbits; D012091:Repetitive Sequences, Nucleic Acid; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D016827:CD8 Antigens; D004337:Drug Carriers; D000939:Epitopes; D008081:Liposomes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan