Comparative Evaluation of Routes of Administration and Efficacy of Monovalent and Bivalent Filarial Vaccine Candidates; BmALT-2 and WbGST

Abstract

Aims: To evaluate immunoprophylactic adequacy of monovalent and bivalent filarial vaccine candidates; BmALT-2 and WbGST through different routes of immunization viz., intramuscular (i.m.), intraperitoneal (i.p.) or subcutaneous (s.c.) way. Study Design:  In vivo and in vitro experimental studies using rodent model of filariasis. Place and Duration of Study: Department of Biochemistry and J B Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India, between June 2016 and July 2017. Methodology: Male Mastomys (n=5-7/group) of 6-8 weeks age were immunized with 25 µg/dose of rBmALT-2, rWbGST, or rBmALT-2+rWbGST per animal along with alum as adjuvant through either of i.m., i.p. or s.c. routes. The control groups of mice received alum only. The protective immunity elicited in the animals was checked by antibody-dependent cellular cytotoxicity and micropore cytotoxicity assay. The splenocytes proliferation and cytokine profile were performed for the appraisal of cellular immune response. Results: Our results demonstrated that immunization through i.m. route is more effective as compared to i.p. or s.c. routes and comparatively monovalent rBmALT-2 induces better protection as compared to monovalent rWbGST or bivalent dose consisting of rBmALT-2+rWbGST. Mastomys immunized through i.m. route with rBmALT-2 alone could induce 77.50% in vitro and 73.28% in vivo cytotoxicity (P<0.05) against Brugia malayi infective larvae (L3), whereas, rWbGST alone and rBmALT-2+rWbGST combined could induce 65% and 68% in vitro and 61% and 65% in vivo cytotoxicity (P<0.05), respectively. Our serological analysis showed that Mastomys immunized i.m. with rBmALT-2 or rWbGST or rBmALT-2+rWbGST induced IgG1, IgG2a and IgG3 antibody response, significantly higher than control groups. The protective effect was found to be associated with a predominantly increased level of IFN-γ and IL-4 in response to rBmALT-2. Conclusion: Intramuscular route is the most effective way of administration of vaccine for better prophylactic response in filariasis. Additionally, co-administration of monovalent vaccine seems to interfere with the prophylactic effect of monovalent rBmALT-2 and rWbGST vaccines.