Immune response studies with Wuchereria bancrofti vespid allergen homologue (WbVAH) in human lymphatic filariasis

Abstract

A homologue of Brugia malayi venom allergen (BmVAH) was cloned from the infective stages (L3) of Wuchereria bancrofti. Sequence analysis showed 90% sequence identity between WbVAH and BmVAH. Recombinant WbVAH was then expressed and purified. VAH from other nematode parasites is being evaluated as potential vaccine candidates. Because W. bancrofti infections are more prevalent than B. malayi, it will significantly benefit using W. bancrofti antigens for vaccine development. In this study, we have evaluated the human immune responses to rWbVAH in putatively immune individuals who live in the endemic regions (endemic normal, EN) to determine the vaccine potential of WbVAH. These responses were then compared to those in infected individuals (microfilaraemic, MF and chronic pathology, CP). Results show that EN subjects carry WbVAH-specific IgG1, IgG2, and IgG3 circulating antibodies. It is interesting to note that CP patients also carried antibodies against WbVAH that was mainly of the IgG3 isotype. Peripheral blood mononuclear cells (PBMC) from EN individuals responded strongly to rWbVAH by proliferating and secreting IFN-γ. PBMC from MF patients also proliferated in response to rWbVAH but secreted mainly IL-10. Thus, there was a clear dichotomy in the cytokine production by infected patients vs individuals who are putatively immune (EN). Although vaccine potential of WbVAH has not been established yet, our findings suggest that WbVAH mediated immune responses in EN individuals is primarily Th1-biased. Further vaccination studies are underway in animal models to determine the role of WbVAH in protective immunity against W. bancrofti and B. malayi infections.

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

“…IgG1, IgG2 and IgG3 isotype levels were found to be higher in EN population against BmAF-Myo and w Bm-LigA recombinant proteins. In several studies involving various recombinant filarial proteins, elevated levels of IgG1, IgG2 and IgG3 isotypes have been reported in putatively immune individuals [14, 33, 36, 44, 45] suggesting their role in filarial larval killing. Nevertheless, polarization of T-helper cell response in EN category towards type 1 or type 2 cannot be specifically be mentioned since it depends upon the type of protein antigen [36, 45].…”

Expression and immune response analysis of Schistosoma japonicum VAL-1, a homologue of vespid venom allergens

“…The SCP family has been found in many parasites (Anand et al 2007;Chalmers et al 2008;Hawdon et al 1996). The widespread occurrence of SCP domain-containing proteins suggests that they may be involved in many important biological processes.…”

Immune responses of B. malayi thioredoxin (TRX) and venom allergen homologue (VAH) chimeric multiple antigen for lymphatic filariasis

“…ASP-1 and ASP-2 (Ancylostoma Secreted Protein) proteins from Onchocerca volvulus have been shown to promote corneal angiogenesis when immunized in mice, signifying that VAH could have a potential role in the pathogenesis (Tawe et al 2000). BmVAH has been consistently showed to be effective as vaccine candidates as single as well as multiple antigen mode in lymphatic filariasis when challenged with B. malayi (Anand et al 2007, Anand et al 2011). It appears to be vital for the survival of parasite in the host (Hawdon et al 1996) and may have a potential role in immune evasion .…”

“…Mouse polyclonal antisera antibodies (1 : 4000 dilution) raised against TV, BmTRX and BmVAH were used as a primary antibody and alkaline phosphatase labelled goat anti-mouse antibody (Bangalore Genei, India) was used as secondary antibody for the analysis of immunoblot. The individual recombinant BmTRX and BmVAH proteins were expressed and Gandhirajan Anugraha et al 470 purified as described earlier (Madhumathi et al 2010, Anand et al 2007.…”