Evaluation of Immune Response Elicited by Inulin as an Adjuvant with Filarial Antigens in Mice Model

Abstract

Filariasis caused by infectious parasitic nematodes has been identified as the second leading source of permanent and long-term disability in Sub-Saharan Africa, Asia and Latin America. Several vaccine candidates were identified from infective third-stage larvae (L3) which involves in the critical transition from arthropod to human. Hitherto studies of these antigens in combination with alum adjuvant have shown to elicit its characteristic Th2 responses. Inulin is a safe, non-toxic adjuvant that principally stimulates the innate immune response through the alternative complement pathway. In the present study, the immune response elicited by inulin and alum as adjuvants were compared with filarial antigens from different aetiological agents: secreted larval acidic protein 1 (SLAP1) from Onchocerca volvulus and venom allergen homologue (VAH) from Brugia malayi as single or as cocktail vaccines in mice model. The study revealed that inulin can induce better humoral response against these antigens than alum adjuvant. Antibody isotyping disclosed inulin's ability to elevate the levels of IgG2a and IgG3 antibodies which mediates in complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC), respectively, in mice. Splenocyte analysis showed that T cells prestimulated with inulin have higher stimulation index (P < 0.05) than alum except for BmVAH antigen. In vitro ADCC assay showed that inulin formulation had induced higher cytotoxicity with filarial antigens (as single P < 0.01 and as cocktail P < 0.05, respectively) than alum. The results had confirmed the capability of inulin to deplete the levels of Treg and brought a balance in Th1/Th2 arms against filarial antigens in mice.

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice

“…Immunizing mice with inulin as the adjuvant with other filarial antigens derived from B . malayi , demonstrated that the adjuvant induced a balanced Th1/Th2 response [ 75 ]. In the present study, a limited Th2 cytokine response and positive IgG1 titers was seen in mice immunized with Ov- 103 and Advax 1 or CpG, yet parasite killing was absent.…”

Cloning, expression and characterization of Brugia malayi abundant larval protein transcript-2 (BmALT-2) expressed in Pichia pastoris

“…Many filarial proteins including secreted larval acidic protein 1 from Onchocerca volvulus, an ALT-2 homologue, have been characterized [47]. A chimeric protein construct comprising thioredoxin, transglutaminase and abundant larval transcript-2 (ALT-2) showed enhanced immunological response [48].…”

Immunological evaluation of fusion protein of Brugia malayi abundant larval protein transcript-2 (BmALT-2) and Tuftsin in experimental mice model

“…Earlier studies showed that protective antibodies can kill filarial parasites by ADCC-mediated mechanism (Chandrashekar et al, 1990; Mahalakshmi et al, 2014). In the in vitro cytotoxicity assay, anti-P-TUFT-ALT-2 and anti-E-ALT-2 sera illustrated higher cytotoxicity as a number of PECs adhered to the straight and dead B. malayi L3 larvae.…”

“…An in vitro ADCC assay was performed against B. malayi L3 larvae by sera of mice immunized with recombinant antigen as described previously (Chandrashekar et al, 1990; Mahalakshmi et al, 2014). Pre-immune sera samples were used as negative control.…”