Immune responses in mice induced by prime-boost schemes of the Plasmodium falciparum apical membrane antigen 1 (PfAMA1)-based DNA, protein and recombinant modified vaccinia Ankara vaccines

摘要

The apical membrane antigen 1 (AMA1) of malaria parasites is a leading vaccine candidate. Its expression in merozoites and sporozoites and its importance for erythrocyte and hepatocyte invasion underline the significance of both humoral and cellular immunities against this antigen in malaria protection. We have generated a DNA construct and a recombinant poxvirus (rMVA) for expressing the Plasmodium falciparum AMA1 ectodomain, produced recombinant AMA1 protein (rAMA1) and evaluated their antigenicity in mice using single and combinatory vaccine schemes. Our results showed that although vaccinations of mice by either DNA or rMVA alone did not yield high antibody responses, they had primed significant numbers of rAMA1-responsive splenocytes. Under heterologous prime-boost schemes, priming with DNA followed by boosting with rMVA or rAMA1 protein resulted in a significant increase in antibody titers. In addition, the antibody titers to AMA1 appeared to be correlated with the levels of inhibition of merozoite invasion of erythrocytes in vitro. Furthermore, different prime-boost schemes resulted in different AMA1-specific antibody isotype (IgG1/IgG2a) ratios, providing us with an indication about Th1 or Th2 responses the vaccination regimens have induced. This study has yielded useful information for further in vivo evaluation of the suitability and effectiveness of the heterologous prime-boost strategy in AMA1 vaccination.