Following the 2016 ECF Consortium annual meeting in May 2016, participants in the project drafted short blog posts about different aspects of their work related to East Coast fever (ECF) vaccine development. This post was contributed by Joana da Silva (University of Maryland), Ivan Morrison (University of edinburgh), Dirk Geysen (ITM Antwerp), George Chaka (CTTBD), Ine de Goeyse (ITM Antwerp) and Kyle Tretina
(University of Maryland).
The Muguga Cocktail, composed of three isolates, is currently being used in the field to vaccinate cattle against East Coast fever. Two recent studies, led by The Roslin Institute, in Scotland, and Institute for Genome Sciences, in the US, unveil its genetic composition in great detail, with implications for both vaccine production and to interpret its protective properties.
The three components of the Cocktail were selected because they differed in their ability to protect against various heterologous challenges, but that in combination they provided protection against a range of cattle-derived isolates.
One of the isolates selected was originally isolated from buffalo, and was serially passaged with the intent to adapt it for transmission in cattle, a necessary trait to produce parasites for inclusion in a vaccine cocktail.
Now, two studies using high-throughput sequencing have revealed that the isolate believed to be derived from buffalo closely resembles one of the other isolates, which is cattle-derived, and that the three isolates together comprise only a small amount of the genetic variation seen in this parasite species.
These observations indicate that a vaccine preparation containing a relatively limited amount of genetic variation, and no buffalo-derived isolate, is sufficient to protect against field challenge from parasites transmitted by cattle.
They also suggest that there is scope to improve the composition of the Cocktail, to simplify the standardization protocol and possibly widen its protective efficacy.
The recent meeting of the East Coast fever consortium, which brings together experts in immunology, parasitology and genomics from three continents (ILRI, Edinburgh, Antwerp, IGS, as well as the organization that produces the infection and treatment method (ITM) vaccine, provided a venue to discuss a way forward.
As a first step, it was suggested that challenge trials be conducted to evaluate the effect of removing one of the two nearly identical cattle isolates. The vaccine stabilate can later be expanded, if needed, to include another isolate that is more divergent antigenically, such as one that originates from a geographic region where parasites are genetically different.
Remixing the cocktail: