Which parasite features can stimulate effective immune responses to infections?
Parasite cell surfaces are constructed with diverse proteins, complex carbohydrates and lipids that are vital for parasite’s transmission, cell invasion, survival in the blood and other body fluids. Collectively, the cell surface is the interface between parasite and host, it mediates the relationship and has a fundamental role in determining whether the relationship is antagonistic or largely peaceful (i.e. virulence).
Studying parasite cell surface proteins is a means of understanding the genetic causes of pathogenesis (how disease is caused) and virulence (how severe it is for the host). The major aspect of this host-parasite interaction is the host’s immune response and cell surface parasite proteins are typically responsible for stimulating (and neutralizing) both innate responses and acquired immunity (i.e. antibodies). So an important motivation for understanding these antigens is to develop them into vaccines, to immunize animals against parasitic disease.
We discover new antigens through a reverse vaccinology approach, using computational approaches to detect tell-tale structural signatures of cell-surface proteins in parasite genomes. These predictions can then be confirmed through experimental approaches such as proteomics and fluorescent in situ microscopy.
For antigens whose surface function is known, such as VSG in trypanosomes and VESA in Babesia parasites, we study how these antigens vary within and between species using phylogenetic methods. This shows us which antigens (or bits of antigens) may be relatively invariant and suitable as universal vaccine targets, and which are highly polymorphic across populations.
Our comparisons of African trypanosome genomes identified a suite of novel antigens, especially in Trypanosoma vivax, in which we have confirmed that they encode abundant proteins, specific to the bloodstream stage. These represent a panel of vaccine candidates that we are exploring through immuno-profiling of natural bovine infections across Africa.
We are also conducting research to develop vaccine candidates from the genomes of bovine trichomonads (Tritrichomonas foetus) and in human malaria parasites (Plasmodium vivax), targeting parasite proteins such as MSP and VIR, which are at the forefront of the host-parasite interface.
Reverse vaccinology has revealed a profusion of plausible antigens that could become potential vaccine candidates. Translating these possibilities into effective solutions is a challenge that requires the collaboration of diverse skills. We are part of the Centre for Global Vaccine Research that aims to bring this collaboration about.