Lymphatic
filariasis causes permanent and long-term disability
worldwide. Lack of potent adulticidal drugs, the emergence of drug
resistance, and the nonavailability of effective vaccines are the
major drawbacks toward LF elimination. However, immunomodulatory proteins
present in the parasite secretome are capable of providing good protection
against LF and thus offer hope in designing new vaccines against LF.
Here, we evaluated the immunogenicity and protective efficacy of B. malayi calreticulin protein (BmCRT) using in
vitro and in vivo approaches. Stimulation
with recombinant BmCRT (rBmCRT) significantly upregulated Th1 cytokine
production in mouse splenocytes, mesenteric lymph nodes (mLNs), and
splenic and peritoneal macrophages (PMΦs). Heightened NO release,
ROS generation, increased lymphocyte proliferation, and increased
antigen uptake were also observed after rBmCRT exposure. Mice immunized
with rBmCRT responded with increased Th1 and Th2 cytokine secretion
and exhibited highly elevated titers of anti-BmCRT specific IgG at
day 14 and day 28 postimmunization while splenocytes and mLNs from
immunized mice showed a robust recall response on restimulation with
rBmCRT. Infective larvae (L3) challenge and protection studies undertaken
in Mastomys coucha, a permissive model for LF, showed
that rBmCRT-immunized animals mounted a robust humoral immune response
as evident by elevated levels of total IgG, IgG1, IgG2a, IgG2b, and
IgG3 in their serum even 150 days after L3 challenge, which led to
significantly reduced microfilariae and worm burden in infected animals.
BmCRT is highly immunogenic and generates robust antiparasitic immunity
in immunized animals and should therefore be explored further as a
putative vaccine candidate against LF.