Plasmodium berghei: relationship between protective immunity and anti-sporozoite (CSP) antibody in mice

Protective immunity and production of anti-sporozoite (CSP) antibody was studied in A/J mice injected with X-irradiated sporozoites using different immunization schedules and antigen doses. Data were also obtained on the immunogenicity of X-irradiated as compared to nonirradiated sporozoites. After a single immunization (1.5 × 10⁵ or 7.5 × 10⁴ X-irradiated sporozoites) a number of animals was completely protected when challenged, but the percentage of protected mice varied considerably from experiment to experiment. Maximal protection was obtained 7 days after the immunization. When the first injection of parasites was followed by a single booster administered 3, 4 or 5 days later, protection was considerably enhanced and the results more consistent. After a single injection of 1.5 × 10⁵ or 7.5 × 10⁴ sporozoites, CSP antibody was detectable from the 19th and 23rd day, respectively, i.e., at a time point when protection was diminishing. This antibody persisted only for a short period. When a single booster was given soon after the first injection, CSP antibody was present in the sera of all the mice from the ninth day on and persisted for greater than 80 days. A single dose of X-irradiated sporozoites injected into rats, induced antibody (CSP) formation which reached a peak after 2 weeks and persisted at this level for more than 3 months. However in rats injected with viable sporozoites, the antibody titers fell rapidly and became undetectable after 4 weeks.From these data we can conclude that (a) the immune response induced by attenuated X-irradiated sporozoites is considerably longer-lasting than that induced by viable sporozoites; (b) CSP antibodies are not detectable during the early stages of the immune response; and (c) protective immunity precedes the presence of detectable serum and antibodies.