An experimental bivalent peptide vaccine against schistosomiasis and fascioliasis

Abstract

With a view to producing peptides capable of inducing a protective immune response against Schistosoma mansoni and Fasciola hepatica, the sequence and structure of the protective antigens Sm14 and Fh15 were analyzed. Their C-termini showed a high level of sequence conservation which, together with models for their three-dimensional structures, aided in peptide selection. Vaccination trials in Swiss mice challenged with S. mansoni cercaria or F. hepatica metacercaria showed that peptides which included the sequences VTVGDVTA or EKNSESKLTQ were capable of inducing levels of protection equivalent to the recombinant form of Sm14. These peptides may represent an alternative to r-Sm14 for the development of a bivalent anti-helminth vaccine.

Introduction

Schistosomes cause chronic disease in millions of young people living in poor countries where their physical health and intellectual capacity are fundamental to national development [1]. Similarly, Fasciola sp., represents a recognized unsolved agricultural problem responsible for economic losses estimated in around US$ 3 billion per year [2] as well as causing a not insignificant number of human infections worldwide. Furthermore, although chemotherapy for both parasites has been available for two decades with influence in reducing morbidity rates, it represents only a palliative measure which leaves the transmission rates unaltered as a consequence of continuous re-infection in endemic areas [3], [4], [5]. Vaccines represent the most attractive long-term alternative to invert this scenario.

Of six vaccine candidates against Schistosoma mansoni initially selected by the WHO [6], [7] four have been subsequently endorsed for scale-up to GMP grade antigen production and phase I/II clinical trials in humans [8]. Two of these, Sh28-GST [9] and Sm14 [10] are closest to reaching this reality with GST already in phase II clinical trials for S. haematobium in Senegal [11] and Sm14 in the final stages of scale-up. Furthermore, Sm14 is the only vaccine candidate to have been shown to afford significant immune protection against both of the above-mentioned helminths. Sm14 is thus an unique opportunity for attacking both the second most prevalent parasitic disease in humans and the most important helminth infection of cattle and therefore represents an attractive strategy for helminth vaccine development [10], [12].

Several attempts have also been made to develop peptide vaccines based on S. mansoni derived antigens [13], [14], [15], [16], [17], [18]. Potential advantages include production cost, chemical stability and safety. Moreover, there is now ample evidence that peptides alone can be immunogenic [19]. Here we describe a strategy which has led to the identification of peptide antigens derived from the vaccine candidate Sm14 with potential applications as bivalent vaccines and as much-needed tools for monitoring vaccine-induced immunity.