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Reverse vaccinology identifies candidates for an improved vaccine against cattle pneumonia in Africa


SosabravoAlfredo_ArtworkByCubanArtist2

Untitled artwork by Cuban artist Alfredo Sosabravo.

‘Mycoplasma mycoides subsp. mycoides (Mmm) is the causative agent of contagious bovine pleuropneumonia (CBPP), a devastating respiratory disease mainly affecting cattle in sub-Saharan Africa. The current vaccines are based on live-attenuated Mmm strains and present problems with temperature stability, duration of immunity and adverse reactions, thus new vaccines are needed to overcome these issues.

‘We used a reverse vaccinology approach to identify 66 Mmm potential vaccine candidates. The selection and grouping of the antigens was based on the presence of specific antibodies in sera from CBPP-positive animals. The antigens were used to immunize male Boran cattle (Bos indicus) followed by a challenge with the Mmm strain Afadé.

‘Two of the groups immunized with five proteins each showed protection after the Mmm challenge (Groups A and C; P < 0.05) and in one group (Group C) Mmm could not be cultured from lung specimens. A third group (Group N) showed a reduced number of animals with lesions and the cultures for Mmm were also negative. While immunization with some of the antigens conferred protection, others may have increased immune-related pathology.’

This is the first report that Mmm recombinant proteins have been successfully used to formulate a prototype vaccine and these results pave the way for the development of a novel commercial vaccine.

ILRI co-author of this paper Joerg Jores makes the following remarks about this success.

‘The International Development Research Centre (IDRC) granted the Vaccine Infectious Disease Organization (VIDO) and the Kenya Agricultural and Livestock Research Organisation (KALRO) a research project to develop a subunit vaccine for CBPP. This project developed successfully and resulted in identification of proteins for a candidate vaccine (Perez Casal et al, 2015, Veterinary Immunology and Immunopathology).

‘At the moment it is not known whether the duration of protection and the efficacy elicited by the recombinant proteins identified are superior to that of the T1/44 live vaccine. A second phase funding from IDRC for VIDO and KALRO will devote efforts to improve and refine the current cocktail subunit vaccine. A subunit vaccine will overcome the need for a cold chain.

‘My ILRI colleague Anne Liljander and I employed ‘reverse vaccinology’—which uses bioinformatics to screen the entire genome of a pathogen to find genes likely to induce protective immune responses in the host animal—to identify 38 Mycoplasma antigens of potential interest (Perez Casal et al, 2015, Veterinary Immunology and Immunopathology). The antigen-encoding genes have been codon optimized, cloned in an expression vector and transferred to VIDO-KALRO.  Two groups of cattle each receiving 5 recombinant antigens showed significant levels of protection compared to the control group. Eight of the 10 of the antigens in the two pools found to be protective were identified by us using the reverse vaccinology approach.’

Graphic_ReverseVaccinology

Graphic from Journal of Clinical Bioinformatics.

Genomics-based antigen selection using reverse vaccinology
‘The reverse approach to vaccine development takes advantage of the recent breakthrough in complete genome sequencing of many bacteria, parasites and viruses. The genome sequence provides a catalogue of all protein antigens that the pathogen can express at any time. Reverse vaccinology is based on in silico prediction of vaccine antigen candidates using the genetic sequence rather than the pathogen itself. This approach allows not only the identification of all antigens seen by conventional methods, but also the discovery of novel antigens that might be less abundant, not expressed in vitro, or less immunogenic during infection that are likely to be missed by conventional approaches (Table 3.1.1). In theory, all genes of a pathogen can be tested without any bias in a high-throughput system to screen for protective immunity.’—Sylvie Bertholet, Steven G Reed and Rino Rappuoli, from Ch 3.1: ‘Reverse vaccinology’, in The Art & Science of Tuberculosis Vaccine Development, 2nd edition.

Read the whole science paper (behind a paywall), Recombinant Mycoplasma mycoides proteins elicit protective immune responses against contagious bovine pleuropneumonia, by Isabel Nkandoa (Kenya Agricultural and Livestock Research Organisation [KALRO]), Jose Perez-Casal (Vaccine Infectious Disease Organization—International Vaccine Centre [VIDO-InterVac]), Martin Mwirigi (KALRO), Tracy Prysliak (VIDO-InterVac), Hugh Townsend (VIDO-InterVac), Emil Berberov (VIDO-InterVac), Joseph Kuria (University of Nairobi), John Mugambi (KALRO), Reuben Soi (KALRO), Anne Liljander (ILRI), Joerg Jores (ILRI), Volker Gerdts, Andrew Potter (VIDO-InterVac), Jan Naessens (ILRI), Hezron Wesonga (KALRO), published in Veterinary Immunology and Immunopathology, Vol 171, Mar 2016.

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