Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi.
While it is known that antibodies are critical for clearance of malaria infections, it is not clear whether adequate antibody responses are maintained and what effect chronic infection has on this response. Here we show that mice with low-grade chronic primary infections of Plasmodium chabaudi or infections very recently eliminated have reduced second infections when compared with the second infection of parasite-free mice. We also show that parasite-specific antibody responses induced by infection of mice with Plasmodium chabaudi contain both short- and long-lived components as well as memory B cells responsible for a faster antibody response during re-infection. Furthermore, parasite-specific antibodies to the C-terminal fragment of merozoite surface protein-1 (MSP-1) undergo avidity maturation. However, antibodies with both low and high avidity persist throughout infection and after re-infection, suggesting repeated rounds of activation and maturation of memory B cells. Neither the avidity profile of the antibody response, nor its maintenance is affected by persisting live parasites. Therefore, differences in parasitemia in re-infection cannot be explained solely by higher levels of antibody or greater affinity maturation of malaria-specific antibodies. These data suggest that there may be an antibody-independent component to the early control of secondary infections in mice that are chronically infected.
Achtman
A H
AH
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
Stephens
R
R
Cadman
E T
ET
Harrison
V
V
Langhorne
J
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D000915:Antibody Affinity; D000953:Antigens, Protozoan / Q000276:immunology; D005260:Female; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000097:blood / Q000276:immunology*; D016788:Plasmodium chabaudi / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D020066:Merozoite Surface Protein 1