| Summary: | Heterologous prime–boost immunization regimens using various vaccine platforms demonstrated promising results against infectious diseases. Here, mice were sequentially immunized with the recombinant baculovirus (rBV), virus-like particle (VLP), and recombinant vaccinia virus (rVV) vaccines expressing the <i>Plasmodium berghei</i> apical membrane antigen 1 (AMA1) for protective efficacy evaluation. The rBV_V_rVV heterologous immunization regimen elicited high levels of parasite-specific IgG, IgG2a, and IgG2b antibody responses in sera. Upon <i>P. berghei</i> challenge infection, proliferations of germinal center B cells in the inguinal lymph nodes, as well as blood CD4<sup>+</sup> and CD8<sup>+</sup> T cells were induced. More importantly, rBV_V_rVV immunization significantly diminished the parasitemia and prevented drastic bodyweight loss in mice post-challenge infection with <i>P. berghei</i>. Our findings revealed that immunization with rBV, VLP, and rVV expressing the AMA1 conferred protection against <i>P. berghei</i> infection, providing evidence for the potential implementation of this strategy.
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