Immune response gene regulation of immunity to Plasmodium berghei sporozoites and circumsporozoite protein vaccines. Overcoming genetic restriction with whole organism and subunit vaccines.
We conducted a series of experiments to define Ir gene regulation of the immune response to Plasmodium berghei sporozoites and circumsporozoite (CS) protein-derived subunit vaccines. The studies demonstrated that there is no apparent genetic restriction of the capacity to develop protective immunity against a large sporozoite challenge after immunization with irradiation-attenuated P. berghei sporozoites; that the Th response to (Asp-Pro-Ala-Pro-Pro-Asn-Ala-Asn)n, the predominant protective B epitope on the P. berghei CS protein, is genetically restricted and regulated by Class II genes (I-Ab) and by genes in the Class I region (H-2Dk) or telomeric to this region; and that this restriction can be overcome by immunization with a r protein including the entire P. berghei CS protein. The results support the development of full length human CS protein vaccines to take advantage of all potential T epitopes on this protein.
Hoffman
S L
SL
Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20814-5055.
Berzofsky
J A
JA
Isenbarger
D
D
Zeltser
E
E
Majarian
W R
WR
Gross
M
M
Ballou
W R
WR
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005802:Genes, MHC Class II; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins; D014612:Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D000954:Antigens, Surface; D010446:Peptide Fragments; D015800:Protozoan Proteins; D014612:Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan