Profiles of Immunoglobulin G Antibody Subclass Responses Specific to MSP3 and UB05 in Plasma of Malaria Negative Children Living in Two Different Agro-ecological Settings of Cameroon

Abstract

Introduction: In malaria endemic areas, antibody specific to promising asexual blood stage malaria vaccine candidates have been demonstrated to play a critical role in protection during sub-clinical malaria. In this context naturally acquired protective immunity is usually driven by blood stage antigen specific IgG antibody subclass responses among which the cytophilic antibody subclasses IgG1 and IgG3 remain the most relevant. Thus, we have assessed IgG antibody subclass responses specific to Plasmodium spp. derived MSP3 and UB05 malaria vaccine candidates, in plasma of children living in areas differing in malaria transmission intensity within Cameroon. Methods: Using MSP3 and UB05 displayed upon the surface of recombinant RNA coliphage Qβ as previously described in our group, IgG antibody subclass responses specific to both immunogens were profiled in plasma from both P. falciparum (Pf) infected and uninfected malaria asymptomatic children. Results: In malaria negative children living in low transmission areas the cytophilic antibody subclasses IgG1 and IgG3 specific to UB05 were significantly higher (P<0.0001) than those specific to MSP3. In contrast IgG1 and IgG3 antibody subclass responses specific to MSP3 were instead significantly higher (P<0.0001 for IgG1; P=0.0007 for IgG3) in their counterparts living in high malaria transmission settings. In asymptomatic Pf infected children living in both areas, whereas IgG1 antibody subclass responses specific to MSP3 was significantly higher (P<0.0001) than the responses specific to UB05, IgG3 antibody subclass responses specific to UB05 was significantly higher (P<0.0001). Conclusion: Thus, there is a differential generation of cytophilic antibody subclasses specific (IgG1 and IgG3) to two classical asexual blood stage antigens in children living within these areas in a malaria endemic region. Whereas for Pf negative children living in low malaria transmission areas UBO5 specific IgG1 and IgG3 correlated best with naturally acquired immunity against malaria; elevated MSP3 targeted cytophilic antibodies were instead prominent in high malaria transmission areas. Thus, repeated exposure to malaria as it is the case with bimodal as against monomodal rainfall areas might be necessary for sustaining high levels of MSP3 specific cytophilic antibodies. This probably tags MSP3 as an unsuitable candidate to measure correlates of protective immunity against malaria.