Recombinant human IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides. Correlation of effect with biologic activity of IL-2.
Current malaria vaccine strategies focus on subunit vaccines that contain one or a limited number of malaria Ag. However, there is widespread nonresponsiveness to many of these Ag probably resulting from Ir gene control. Using a congenic mouse model, we demonstrated that human rIL-2 (as an adjuvant) can overcome Ir gene controlled low immune responsiveness to peptide malaria Ag vaccine candidates [R32tet32, R32LR, and Th2R-NP (NANP)5NA] as determined by the antibody response, providing it is emulsified with the Ag during immunization. This effect is not caused by IL-2 merely acting as a foreign protein and stimulating noncognate help; it requires biologic activity of the IL-2, as determined by studying the effect of inactive rIL-2, which has minimal biologic activity but which has retained its antigenicity. IL-2 does not appear to be working by an effect on priming of specific Th, and IL-2 cannot overcome an Ir gene controlled low T cell proliferative response. IL-2 may have a role to play in human vaccine development where a high titer antibody response to a subunit vaccine is required.
Good
M F
MF
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Pombo
D
D
Lunde
M N
MN
Maloy
W L
WL
Halenbeck
R
R
Koths
K
K
Miller
L H
LH
Berzofsky
J A
JA
D000818:Animals; D000954:Antigens, Surface / Q000008:administration & dosage* / Q000276:immunology; D005802:Genes, MHC Class II / Q000187:drug effects*; D006183:H-2 Antigens / Q000235:genetics*; D006801:Humans; D007117:Immunization, Secondary; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000954:Antigens, Surface; D006183:H-2 Antigens; D007376:Interleukin-2; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan