Abstract
Lymphatic filariasis (LF) is a tropical parasitic infection of human transmitted by mosquitoes. Chronic infection results in severe physical disability in the infected patients. Although several potential vaccine antigens were identified by several groups, there are no licensed prophylactic vaccine to date against this infection in the human. Previous attempts from our laboratory to develop a trivalent prophylactic vaccine against LF showed that >90% protection could be achieved in rodent models. However, this trivalent vaccine gave only 35% protection in non-human primates. The major focus of this study was to develop a tetravalent prophylactic vaccine (rBmHAXT) and test the vaccine potential in a mouse model. We evaluated three different adjuvant formulations; alum, glucopyranosyl lipid adjuvant in stable emulsion (GLA/SE) alum (AL019), and mannosylated chitosan (MCA) to determine the optimum adjuvant formulation for rBmHAXT. Results presented in this study show that rBmHAXT + AL019 gave the highest rate of protection (>88%) against challenge infection, compared to rBmHAXT + AL007 (79%), rBmHAXT + MCA (79%) and controls. Analysis of the immune correlates of protection showed that all three adjuvants elicited high titer of antigen-specific IgG1, IgG2a, and IgG2b antibodies. High number of IFN-γ-producing antigen-specific memory cells were generated in the vaccinated animals irrespective of the adjuvants used. Similarly, spleen cells from rBmHAXT-vaccinated animals secreted IL-4, IL-10, and IFN-γ in response to rBmHAXT suggesting the generation of a balanced Th1/Th2 response. There was also an increase in IL-17-secreting cells in rBmHAXT-vaccinated animals. These findings thus suggest that rBmHAXT + AL019 is a better prophylactic formulation for LF.
Highlights
Lymphatic filariasis (LF) is a neglected tropical parasitic disease caused by three filarial parasites, Wuchereria bancrofti, Brugia malayi, and Brugia timori and is transmitted by mosquitoes
In rBmHAXT + mannosylated chitosan (MCA) group where all the doses were given orally, we found there was very little titer of antigen-specific antibodies nearly same as AL007, AL019, and MCA adjuvant control groups (Figure 2A)
Results presented in this study show that both AL007 and AL019 (GLA + alum) are excellent adjuvants for rBmHAXT immunization in mice
Summary
Lymphatic filariasis (LF) is a neglected tropical parasitic disease caused by three filarial parasites, Wuchereria bancrofti, Brugia malayi, and Brugia timori and is transmitted by mosquitoes. According to the World Health Organization, currently 856 million people residing in 52 countries require preventive chemotherapy to stop the spread of infection [1,2,3,4]. Preventive chemotherapy is still needed in all other countries endemic for this disease and has not achieved the desired levels of coverage as of 2017 [6, 7]. As in Sri Lanka, there is fear of reemergence of the infection in areas where MDA was given, mainly due to subject noncompliance [8,9,10,11]. Prophylactic vaccination with MDA will be a more sustainable and long lasting approach to eliminate infection from a community by eliciting herd immunity [2]
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