Immunity & infection
Lymphatic filariasis currently affects 120 million people around the world and another 1.2 billion people are at risk. An effective prophylactic vaccine is needed to control and eliminate the infection from 72 countries that are endemic for this disease. In this study we compared and evaluated the immunogenicity and efficacy of two multivalent fusion proteins (rBmHAT and rBmHAXT) for their ability to protect rhesus macaques against challenge infections with Brugia malayi. A total of 40 macaques were divided into three treatment groups and one control group (N=10/group). Two different adjuvants, alum and alum adsorbed TLR-4 agonist (AL019) were used in this study at 2 mg/ml. vaccinated animals received four immunizations (days 0, 28, 56 and 84) with 1.5mg/ml of rBmHAT+alum, rBmHAT+AL019 or rBmHAXT+AL019. Control animals received AL019 only. One month after the last dose, all macaques were challenged subcutaneously with 130-180 third stage larvae of B. malayi. Our results show that all vaccinated macaques developed significant (p≤0.003) titers of antigen-specific IgG antibodies (1:20,000) compared to controls. Specifically, levels of antigen-specific IgG1 and IgG2 antibodies were significantly (p≤0.01) increased. Analysis of the PBMCs, demonstrated increases in IL-4 and IFNγ secreting effector memory T cells in vaccinated animals. Challenge results showed that 60% of macaques vaccinated with rBmHAT+AL019 and 50% of macaques vaccinated with rBmHAXT+AL019 did not show any signs of infection or lymphatic pathology until week 18 after infection (end of the experiment). These studies demonstrate that rBmHATor rBmHAXT in combination with AL019 are promising vaccine candidates against lymphatic filariasis.
Post-doctoral Research Associate
university of illinois
Professor of Microbiology and Immunology, Head of
University of Illinois