Lymphatic filariasis (LF) affects 120 million people around the world and another 856 million people are at risk of acquiring the
infection.
Mass Drug Administration (MDA) spearheaded by the World Health Organization is the only current strategy to control this
infection. Recent reports suggest that despite several rounds of MDA, elimination has not been achieved and there is a need for more stringent control strategies for control of LF. An effective prophylactic
vaccine combined with MDA has significant potential. Initial trials using a prophylactic trivalent recombinant Brugia malayi
heat shock protein 12.6, abundant larval transcript -2 and
tetraspanin large extra-cellular loop (rBmHAT)
vaccine developed in our laboratory conferred only 35% protection in macaques. Therefore, the focus of the present study was to improve the current
vaccine formulation to obtain better protection in non-human primates. We made two modifications to the current formulation: (i) the addition of another
antigen,
thioredoxin peroxidase-2 (TPX-2) to make it a
tetravalent vaccine (rBmHAXT) and (ii) the inclusion of an adjuvant; AL019 (
alum plus glucopyranosyl
lipid adjuvant-stable
emulsion) that is known to promote a balanced Th1/Th2 response. A double-blinded vaccination trial was performed with 40 macaques that were divided into three treatment groups and one control group (n = 10/group). Vaccinated animals received 4 immunisations at 1 month intervals with 150 µg/ml of rBmHAT plus
alum, rBmHAT plus AL019 or rBmHAXT plus AL019. Control animals received AL019 only. All vaccinated macaques developed significant (P ≤ 0.003) titers of
antigen-specific
IgG antibodies (1:20,000) compared with the controls. One month after the last dose, all macaques were challenged s.c. with 130-180 B. malayi L3s. Our results showed that seven out of 10 (70%) of macaques given the improved rBmHAXT
vaccine did not develop the
infection compared with AL019 controls, of which seven out of 10 macaques developed the
infection. Titers of
antigen-specific
IgG1 and
IgG2 antibodies were significantly (P ≤ 0.01) higher in vaccinated animals and there was an increase in the percentage of
IL-4 and IFN-γ secreting
antigen-responding memory T cells. These studies demonstrated that the improved formulation (rBmHAXT plus AL019) is a promising
vaccine candidate against human
lymphatic filariasis.