Enhanced Humoral Response Induced against Plasmodium falciparum Asexual Blood Stage Immunogens in Mice after Complementary DNA Primed-Recombinant Hybrid Qβ Phage Boost

Author(s): Abel Lissom, Lawrence Ayong, Josué Simo, Thibau Flaurant Tchouangueu, Loveline Ngu, Jules Colince Tchadji, Sylvie Kemleu, Georgia Ambada, Carole Stephanie Sake, Herve F. Ouambo, Rosette Megnekou, Lazard Kaptue, Alain Bopda Waffo, Chae Gyu Park, Godwin W. Nchinda

Dendritic cells are vital in the initiation and regulation of immune responses against invading pathogens. Here we asked whether the immune response against asexual blood stage malaria can be improved by combining DNA vaccine targeting UB05-MSP3 to the dendritic cells in situ with a recombinant QβUB05MSP3 hybrid phage boost. We generated a DNA vaccine candidate encoding for fusion of Plasmodium falciparum UB05MSP3 antigens and single-chain antibody specific to antigen uptake receptor DEC-205 expressed on both mouse and human DCs (scDEC205). DNA vaccine (scDEC205-UB05MSP3) was administrated in mice by conventional intramuscular injection. Animals were boosted intranasally either with recombinant QβUB05, QβMSP3 or QβUB05MSP3 phage. The parasite invasion inhibition assay was done using mice antisera against 3D7 Plasmodium falciparum strain. The reactivity of specific IgA and IgG subclasses were determined by ELISA. The complementary prime-boost immunization with DNA and QβUB05MSP3 induced more pilly potent antibody response that resulted to two time more effective parasite invasion inhibition than the monoclonal antibodies (positive control) and antisera of others mice groups (P<0.0001). The mice boosted with QβUB05MSP3 phage had significantly higher IgA and IgG antibody responses than those boosted with DNA, QβUB05 or QβMSP3 (P <0.01). The significantly higher reactivities of IgG2b and IgG3 against MSP3 and UB05 antigens separately were shown in QβUB05MSP3 and QβUB05 boosted mice compared to the others groups (p< 0.05). These findings showed that complementary QβUB05MSP3 hybrid phage boost vaccination enhances plasmid DNA immunogenicity of asexual blood stage antigen, resulting to an effective parasite invasion inhibition through a significant reactivity of IgG2b and IgG3 antibody against surface antigens.

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