Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine.
The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.
Tian
J H
JH
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Miller
L H
LH
Kaslow
D C
DC
Ahlers
J
J
Good
M F
MF
Alling
D W
DW
Berzofsky
J A
JA
Kumar
S
S
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005805:Genes, MHC Class I; D005982:Glutathione Transferase; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology*; D007109:Immunity / Q000235:genetics; D007116:Immunization, Passive; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013045:Species Specificity
D000954:Antigens, Surface; D006183:H-2 Antigens; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D005982:Glutathione Transferase