Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenicity of a peptide malaria vaccine in Aotus monkeys.
Synthetic peptide and recombinant protein vaccines are optimally immunogenic when delivered with an effective adjuvant. Candidate vaccines currently insufficiently immunogenic may induce a protective immunity if they could be delivered with more effective adjuvants. For example, immunogens that induce promising responses when administered to mice with complete and incomplete Freund's adjuvants perform less well in primate animal models where complete Freund's adjuvant is not used. We report the use of synthetic oligodeoxynucleotides containing CpG motifs, the sequences of which are based on immunostimulatory bacterial DNA sequences, to enhance the immune response in Aotus monkeys to a synthetic peptide malaria vaccine. Monkeys were immunized with the synthetic peptide PADRE 45, a synthetic peptide containing amino acid sequences derived from the circumsporozoite protein (CSP) from Plasmodium falciparum, and delivered in an emulsion of saline and Montanide 720, a mannide oleate in oil solution, that also contained one of three oligodeoxynucleotides. The animals receiving oligodeoxynucleotides containing either three or four CpG motifs produced antibodies that bound a recombinant CSP as measured in ELISA, and reacted with P. falciparum sporozoites in a sporozoite immunofluorescent test. These responses were significantly greater than those seen in animals receiving the oligodeoxynucleotide without CpG motifs. These data indicate that oligodeoxynucleotides containing CpG motifs improve immunogenicity of peptide immunogens in non-human primates, and may be immunopotentiators useful in humans.
Jones
T R
TR
Malaria Program, Naval Medical Research Center, Bethesda, MD 20852, USA. jonest@nmripo.nmri.nnmc.navy.mil
Obaldia
N
N
Gramzinski
R A
RA
Charoenvit
Y
Y
Kolodny
N
N
Kitov
S
S
Davis
H L
HL
Krieg
A M
AM
Hoffman
S L
SL
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D016645:Aotidae; D018899:CpG Islands / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D009841:Oligonucleotides; C401223:PADRE 45; D010455:Peptides; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan