EVALUATION OF PROPHYLACTIC ADEQUACY OF FILARIAL RECOMBINANT PROTEIN (rBmALT-2) WITH MONOPHOSPHORYL LIPID A (MPLA) ADJUVANT

Brugia malayi Abundant larval transcript-2 (BmALT-2) is most potential prophylactic vaccine candidate. In order to increase the protection efcacy of BmALT-2, Monophosphory Lipid A (MPLA), as adjuvant, a detoxied derivative of lipopolysaccharide (LPS) known to promote Th-1 responses, was used in this study. Moreover to determine the percentage of protection obtained following a challenge infection with B. malayi L3 larvae in immunized Mastomys. This study used, 6-8 weeks aged healthy Mastomys (n=5-7/group), immunized intramuscularly with 50 μg of rBmALT-2 antigen either with MPLA or Alum as adjuvant and the control groups received MPLA or Alum only. The protective immunity elicited in the Mastomys was checked by in vitro antibody-dependent cellular cytotoxicity (ADCC) and in vivo micropore chamber assay. The humoral and cellular immune responses were also analyzed. Our results demonstrate, high antibody response in all immunized group compared to control group. We observed increased levels of IgG2a and IgG2b antibodies in rBmALT-2+MPLA and rBmALT-2+Alum+MPLA immunized group, whereas, rBmALT-2+Alum immunized group generated IgG1, IgG2a and IgG3 antibodies. rBmALT-2+Alum group secreted high levels of IL-4 and IFN-γ cytokines and suggesting the balanced Th-1/Th-2 response. The increased level of IL-10 cytokine in rBmALT-2+MPLA or rBmALT2+Alum+MPLA groups reecting the inhibitory effect of Th-1 (IFN-γ) and Th-2 (IL-4) cytokines which do not demonstrate the classical role of ; MPLA. Furthermore our, in vitro and in vivo assay results observed signicantly high cytotoxicity in rBmALT-2+Alum group in vitro (80% p<0.001) and in vivo (79.79%; p<0.001) compared to rBmALT-2+MPLA and rBmALT-2+Alum+MPLA in vitro 61% and 67% and in vivo 59.84% and 65.96% cytotoxicity. This study illustrated immunomodulation, which includes an up-regulation of IL-10 cytokine and a decreased expression of TLR-4 (MPLA) by which larial parasites have evolved to escape host immune mechanisms.