Biological activities of anti-merozoite surface protein-1 antibodies induced by adjuvant-assisted immunizations in mice with different immune gene knockouts

Abstract

Immunizations with Plasmodium falciparum MSP1-42 or MSP1-19 induce antibodies that inhibit parasites in vitro, which correlates with in vivo protective immunity by vaccination. We previously showed that several adjuvant formulations can induce anti-MSP1-19 antibodies in interleukin-6, intercellular adhesion molecule 1, CD80, and CD86 knockout (KO) mice and at levels similar to those obtained in the healthy uninfected hosts. Here, we determine whether these immune gene KOs or the immunopotentiating activities of the adjuvants have a more important influence on the induction of parasite-inhibitory anti-MSP1-19 antibodies. Results showed that the biological activities of the anti-MSP1-19 antibodies induced by these adjuvants were not affected by the immune gene KOs. All adjuvant formulations that induced significant inhibitory antibody responses (i.e., >50% inhibition of parasite growth) contained monophosphoryl lipid A (MPL) in emulsion carriers, whereas MPL or emulsion carriers alone were ineffective. The ability to retain vaccine efficacy by the MSP1-19 and adjuvant formulations in the altered immunological background is a valuable and significant attribute in light of many instances of skewed immune status in the targeted vaccine populations.

FIG. 1.

Relationship between ELISA anti-MSP1-19 titer and the degree of parasite growth inhibition of anti-MSP1-19 antibodies induced by different adjuvant formulations in WT, IL-6 KO, CD80 KO, CD86 KO, and ICAM-1 KO mice. Data are segregated into two groups represented by filled circles and open circles having parasite growth inhibition of >50% and <50%, respectively. Antibodies induced by the adjuvants ISA720-MPL, ISA720-QS21-MPL, and MPL-SE (filled circles) and antibodies induced by the adjuvants ISA720, MF59, QS21, ISA720-QS21, and MPL-AF (open circles) are shown. Regression lines (solid lines) for each of the two groups of data are shown with 95% confidence limits (dashed lines). A regression line (dotted pattern) for the entire combined data set is also shown.