ILRI vaccine biosciences program outputs

Permanent URI for this collectionhttps://hdl.handle.net/10568/33329

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Navigating upstream-downstream animal health research: Reflections from the Livestock and Fish Program
(Brief, 2016-12) Wieland, Barbara; Mohan, Chadag V.; Nene, Vishvanath M.; Toye, Philip G.
Identification and the preliminary in vitro characterization of IRIS homologue from salivary glands of Ixodes persulcatus Schulze
(Journal Article, 2016-02) Toyomane, K.; Konnai, S.; Niwa, A.; Githaka, Naftaly W.; Isezaki, M.; Yamada, S.; Ito, T.; Takano, A.; Ando, S.; Kawabata, H.; Murata, S.; Ohashi, K.
Ixodes ricinus immunosuppressor (Iris) is a tick salivary gland protein derived from I. ricinus. In this study, Iris homolog was identified in the salivary glands of Ixodes persulcatus, which is the specific vector of the Lyme disease agent in Japan. The homolog was named Ipis-1. To investigate the function of Ipis-1, we prepared a recombinant Ipis-1 expressed in COS-7 cells as a rabbit IgG Fc-fused protein (Ipis-1-Ig). Cell proliferation assay and IFN-γ ELISA showed that Ipis-1-Ig inhibits the proliferation and IFN-γ production of bovine peripheral blood mononuclear cells (PBMCs). Notably, Ipis-1-Ig inhibited the cell proliferation and production of IFN-γ in bovine PBMCs even when CD14+ cells were depleted, suggesting that Ipis could directly interact with T cells and inhibit their functions. In conclusion, Ipis could contribute to the establishment of environments suitable for tick blood feeding and pathogen transmission by suppressing the function of immune cells.
Evaluation of a topical formulation of eprinomectin against Anopheles arabiensis when administered to Zebu cattle (Bos indicus) under field conditions
(Journal Article, 2016-12) Lozano Fuentes, S.; Kading, R.C.; Hartman, D.A.; Okoth, Edward A.; Githaka, Naftaly W.; Nene, Vishvanath M.; Poché, R.M.
Background Although vector control strategies, such as insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) have been effective in Kenya the transmission of malaria continues to afflict western Kenya. This residual transmission is driven in part by Anopheles arabiensis, known for its opportunistic blood feeding behaviour and propensity to feed outdoors. The objective of this research was to evaluate the efficacy of the drug eprinomectin at reducing malaria vector density when applied to cattle (Bos indicus), the primary source of blood for An. arabiensis, under field conditions. Methods A pilot study was carried out in the Samia District of western Kenya from September to October of 2014. Treatment and control areas were randomly designated and comprised of 50 homes per study area. Before cattle treatments, baseline mosquito counts were performed after pyrethrum spray. Cows in the treatment area were administered topical applications of eprinomectin at 0.5 mg/kg once a week for two consecutive weeks. Mosquito collections were performed once each week for two weeks following the eprinomectin treatments. Mosquitoes were first identified morphologically and with molecular confirmation, then screened for sporozoite presence and host blood using PCR-based methods. Results The indoor resting density of An. arabiensis was significantly reduced by 38 % in the treatment area compared to the control area at one-week post-treatment (Control mean females per hut = 1.33 95 % CI [1.08, 1.64]; Treatment = 0.79 [0.56, 1.07]). An increase in the indoor resting density of Anopheles gambiae s.s. and Anopheles funestus s.s. was observed in the treatment area in the absence of An. arabiensis. At two weeks post-treatment, the total number of mosquitoes for any species per hut was not significantly different between the treatment and control areas. No change was observed in An. arabiensis host preference as a result of treatment. Conclusions Systemic drugs may be an important tool by which to supplement existing vector control interventions by significantly impacting outdoor malaria transmission driven by An. arabiensis through the treatment of cattle.
Access to livestock health interventions and products in dairy and cattle value chains in Tanzania
(Brief, 2016-12) Kiara, Henry K.; Steinaa, Lucilla; Svitek, Nicholas; Schieck, Elise G.; Toye, Philip G.
Pig vaccines and diagnostics for African swine fever in Uganda
(Brief, 2016-12-30) Steinaa, Lucilla; Bishop, Richard P.; Okoth, Edward A.; Svitek, Nicholas; Riitho, V.
ILRI Tick Unit: Local research with global impact
(Poster, 2016-10) Githaka, Naftaly W.; Mwaura, S.; Nene, Vishvanath M.
Interventions and tools to improve small ruminant health in Ethiopia
(Brief, 2016-12) Gemeda, B.; Desta, Hiwot; Roesel, Kristina; Okoth, Edward A.; Secchini, F.; Liljander, Anne M.; Wieland, Barbara
Pig diseases in Uganda: Impacts on pig production, human health and nutrition
(Brief, 2016-12) Dione, Michel M.; Steinaa, Lucilla; Okoth, Edward A.; Roesel, Kristina; Wieland, Barbara
Approaches to vaccination against Theileria parva and Theileria annulata
(Journal Article, 2016-12) Nene, Vishvanath M.; Morrison, W. Ivan
Despite having different cell tropism, the pathogenesis and immunobiology of the diseases caused by Theileria parva and Theileria annulata are remarkably similar. Live vaccines have been available for both parasites for over 40 years, but although they provide strong protection, practical disadvantages have limited their widespread application. Efforts to develop alternative vaccines using defined parasite antigens have focused on the sporozoite and intracellular schizont stages of the parasites. Experimental vaccination studies using viral vectors expressing T. parva schizont antigens and T. parva and T. annulata sporozoite antigens incorporated in adjuvant have, in each case, demonstrated protection against parasite challenge in a proportion of vaccinated animals. Current work is investigating alternative antigen delivery systems in an attempt to improve the levels of protection. The genome architecture and protein-coding capacity of T. parva and T. annulata are remarkably similar. The major sporozoite surface antigen in both species and most of the schizont antigens are encoded by orthologous genes. The former have been shown to induce species cross-reactive neutralizing antibodies, and comparison of the schizont antigen orthologues has demonstrated that some of them display high levels of sequence conservation. Hence, advances in development of subunit vaccines against one parasite species are likely to be readily applicable to the other.
Complete genome sequence of Mycoplasma mycoides subsp. mycoides T1/44, a vaccine strain against contagious bovine pleuropneumonia
(Journal Article, 2016-04-28) Gourgues, G.; Barre, A.; Beaudoing, E.; Weber, J.; Magdelenat, G.; Barbe, V.; Schieck, Elise G.; Jores, Joerg; Vashee, S.; Blanchard, Alain; Lartigue, C.; Sirand-Pugnet, P.
Mycoplasma mycoides subsp. mycoides is the etiologic agent of contagious bovine pleuropneumonia. We report here the complete genome sequence of the strain T1/44, which is widely used as a live vaccine in Africa.
Differential infection patterns and recent evolutionary origins of equine hepaciviruses in donkeys
(Journal Article, 2017-01) Walter, S.; Rasche, A.; Moreira-Soto, A.; Pfaender, S.; Bletsa, M.; Corman, V.M.; Aguilar-Setien, A.; García Lacy, F.; Hans, A.; Todt, D.; Schuler, G.; Shnaiderman-Torban, A.; Steinman, A.; Roncoroni, C.; Venezian, V.; Rusenova, N.; Sandev, N.; Rusenov, A.; Zapryanova, D.; García Bocanegra, I.; Jores, Joerg; Carluccio, A.; Veronesi, M.C.; Cavalleri, J.M.V.; Drosten, C.; Lemey, P.; Steinmann, E.; Drexler, J.F.
The hepatitis C virus (HCV) is a major human pathogen. Genetically related viruses in animals suggest a zoonotic origin of HCV. The closest relative of HCV is found in horses (termed equine hepacivirus, EqHV). However, low EqHV genetic diversity implies relatively recent acquisition of EqHV by horses, making a derivation of HCV from EqHV unlikely. To unravel the EqHV evolutionary history within equid sister species, we analyzed 829 donkeys and 53 mules sampled in nine European, Asian, African and American countries by molecular and serologic tools for EqHV infection. Antibodies were found in 278 animals (31.5%), and viral RNA was found in 3 animals (0.3%), all of which were simultaneously seropositive. A low RNA prevalence in spite of high seroprevalence suggests predominance of acute infection, a possible difference from the mostly chronic hepacivirus infection pattern seen in horses and humans. Limitation of transmission due to short courses of infection may explain the existence of entirely seronegative groups of animals. Donkey and horse EqHV strains were paraphyletic and 97.5-98.2% identical in their translated polyprotein sequences, making virus/host co-speciation unlikely. Evolutionary reconstructions supported host switches of EqHV between horses and donkeys without the involvement of adaptive evolution. Global admixture of donkey and horse hepaciviruses was compatible with anthropogenic alterations of EqHV ecology. In summary, our findings do not support EqHV as the origin of the significantly more diversified HCV. Identification of a host system with predominantly acute hepacivirus infection may enable new insights into the chronic infection pattern associated with HCV.
Link of a ubiquitous human coronavirus to dromedary camels
(Journal Article, 2016-08-30) Corman, V.M.; Eckerle, I.; Memish, Z.A.; Liljander, Anne M.; Dijkman, R.; Jonsdottir, H.; Ngeiywa, K.J.Z.J.; Kamau, E.; Younan, M.; Al Masri, M.; Assiri, A.; Gluecks, Ilona V.; Musa, B.E.; Meyer, B.; Müller, M.A.; Hilali, Mosaad; Bornstein, S.; Wernery, U.; Thiel, V.; Jores, Joerg; Drexler, J.F.; Drosten, C.
The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses’ evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV–infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.
Analyses of mitochondrial genes reveal two sympatric but genetically divergent lineages of Rhipicephalus appendiculatus in Kenya
(Journal Article, 2016-12) Kanduma, Esther G.; Mwacharo, Joram M.; Githaka, Naftaly W.; Kinyanjui, P.W.; Njuguna, J.; Kamau, L.M.; Kariuki, E.; Mwaura, S.; Skilton, Robert A.; Bishop, Richard P.
Background The ixodid tick Rhipicephalus appendiculatus transmits the apicomplexan protozoan parasite Theileria parva,which causes East coast fever (ECF), the most economically important cattle disease in eastern and southern Africa. Recent analysis of micro- and minisatellite markers showed an absence of geographical and host-associated genetic sub-structuring amongst field populations of R. appendiculatus in Kenya. To assess further the phylogenetic relationships between field and laboratory R. appendiculatus tick isolates, this study examined sequence variations at two mitochondrial genes, cytochrome c oxidase subunit I (COI) and 12S ribosomal RNA (rRNA), and the nuclear encoded ribosomal internal transcribed spacer 2 (ITS2) of the rRNA gene, respectively. Results The analysis of 332 COI sequences revealed 30 polymorphic sites, which defined 28 haplotypes that were separated into two distinct haplogroups (A and B). Inclusion of previously published haplotypes in our analysis revealed a high degree of phylogenetic complexity never reported before in haplogroup A. Neither haplogroup however, showed any clustering pattern related to either the geographical sampling location, the type of tick sampled (laboratory stocks vs field populations) or the mammalian host species. This finding was supported by the results obtained from the analysis of 12S rDNA sequences. Analysis of molecular variance (AMOVA) indicated that 90.8 % of the total genetic variation was explained by the two haplogroups, providing further support for their genetic divergence. These results were, however, not replicated by the nuclear transcribed ITS2 sequences likely because of recombination between the nuclear genomes maintaining a high level of genetic sequence conservation. Conclusions COI and 12S rDNA are better markers than ITS2 for studying intraspecific diversity. Based on these genes, two major genetic groups of R. appendiculatus that have gone through a demographic expansion exist in Kenya. The two groups show no phylogeographic structure or correlation with the type of host species from which the ticks were collected, nor to the evolutionary and breeding history of the species. The two lineages may have a wide geographic distribution range in eastern and southern Africa. The findings of this study may have implications for the spread and control of R. appendiculatus, and indirectly, on the transmission dynamics of ECF.
Proteomics of Theileria parva sporozoites
(Poster, 2016-05-22) Nyagwange, James; Ternette, Nicola; Tijhaar, Edwin; Pelle, Roger; Nene, Vishvanath M.
Discovery of novel CTL epitopes by peptide library screening of CTL lines from Theileria parva immune animals
(Poster, 2016-05-22) Svitek, Nicholas; Saya, R.; Awino, Elias; Nielsen, Morten; MacHugh, Niall D.; Silva, Joana C.; Nene, Vishvanath M.; Steinaa, Lucilla
Immunogenicity and protection of the Theileria parva CTL antigen Tp1, with or without a leader sequence, using HAd5/MVA prime-boost vaccination
(Poster, 2016-05-22) Svitek, Nicholas; Saya, R.; Awino, Elias; Gilbert, S.C.; Poole, Elizabeth J.; Nene, Vishvanath M.; Steinaa, Lucilla
Hepatitis E virus infection in dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983–2015
(Journal Article, 2016-07) Rasche, A.; Saqib, M.; Liljander, Anne M.; Bornstein, S.; Zohaib, A.; Renneker, S.; Steinhagen, K.; Wernery, R.; Younan, M.; Gluecks, Ilona V.; Hilali, Mosaad; Musa, B.E.; Jores, Joerg; Wernery, U.; Drexer, J.F.; Drosten, C.; Corman, V.M.
A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. We screened 2,438 dromedary samples from Pakistan, the United Arab Emirates, and 4 African countries. HEV-7 is long established, diversified and geographically widespread. Dromedaries may constitute a neglected source of zoonotic HEV infections.
Vaccines and diagnostics—The case for regional One Health centres of excellence
(Presentation, 2016-05-31) Grace, Delia; Toye, Philip G.; Tarawali, Shirley A.; Nene, Vishvanath M.
Extensive polymorphism of Ra86 genes in field populations of Rhipicephalus appendiculatus from Kenya
(Journal Article, 2016-07) Kamau, L.M.; Skilton, Robert A.; Githaka, Naftaly W.; Kiara, Henry K.; Kabiru, E.; Shah, Tushaar; Musoke, A.J.; Bishop, Richard P.
Commercial vaccines based on recombinant forms of the Bm86 tick gut antigen are used to control the southern cattle tick, Rhipicephalus microplus, a 1-host species, in Australia and Latin America. We describe herein sequence polymorphism in genes encoding Ra86 homologues of Bm86 in the brown ear tick, Rhipicephalus appendiculatus, isolated from four Kenyan field populations and one laboratory colony. Sequencing of 19 Ra86 sequences defined two alleles differentiated by indels, encoding 693 amino acids (aa) and 654 aa respectively, from the Muguga laboratory reference strain. Ra86 sequences were also determined from gut cDNA from four field populations of R. appendiculatuscollected in different livestock production systems in Kenya. Analysis of approximately 20 Ra86 sequences from each of the four field sites in central and Western Kenya; Makuyu, Kiambu, Kakamega and Uasin Gishu, revealed three additional size types differentiated by 39–49 amino acid indels resulting in a total of 5 indel-defined genotypes. The 693 aa type 5 was isolated only from the laboratory tick stock; genotypes 1, 2 and 3 were identified in ticks from the four Kenyan field sites and appeared to be derivatives of the shorter RA86 genotype found in Muguga laboratory stock genotype 4. By contrast no large indels have yet been observed between R. microplus sequences from Australia, South America or Africa. Evidence that selection contributes to the observed sequence variation was provided by analysis of ratio of synonymous and non-synonymous substitutions and application of the selective neutrality and neutral evolution tests to the primary data. Phylogenetic analysis clustered sequences from all Ra86 size types and Bm86, into four major clades based on amino acid substitutions, but there was no evidence that these groupings correlated with geographical separation of R. appendiculatus populations
Recombinant Mycoplasma mycoides proteins elicit protective immune responses against contagious bovine pleuropneumonia
(Journal Article, 2016-03) Nkando, I.; Pérez Casal, J.; Mwirigi, M.; Prysliak, T.; Townsend, H.; Berberov, E.; Kuria, J.; Mugambi, J.; Soi, R.; Liljander, Anne M.; Jores, Joerg; Gerdts, V.; Potter, A.; Naessens, Jan; Wesonga, H.O.
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 Mmmstrains 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.

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