Attenuated vaccines for tropical theileriosis, babesiosis and heartwater: the continuing necessity

Shkap, Varda; Vos, A.J. De; Zweygarth, E.; Jongejan, Frans

doi:10.1016/j.pt.2007.07.003

Cited by 82 publications

(72 citation statements)

References 47 publications

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“…It is not inconceivable that the shared characteristics of Babesia and Plasmodium may make genetically modified Babesia an attractive agent for delivery of live antimalaria vaccines. Such thoughts are encouraged by the fact that Babesia has been successfully used as an attenuated vaccine in veterinary applications (42).…”

Section: Cd14mentioning

confidence: 99%

Suppression ofPlasmodium cynomolgiin Rhesus Macaques by Coinfection withBabesia microti

Duivenvoorde¹,

Wel²,

Werff³

et al. 2010

Infect Immun

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Both Plasmodium and Babesia species are intraerythrocytic protozoans that infect a wide range of hosts, including humans, and they elicit similar inflammatory responses and clinical manifestations that differ markedly in severity. We recently reported that a rhesus macaque that was chronically infected with Babesia microti was able to control infection with Plasmodium cynomolgi (a parasite of macaques with characteristics very similar to those of Plasmodium vivax) better than naïve monkeys. To confirm this and to investigate the underlying immunopathology, six naïve rhesus monkeys were infected with B. microti. After 24 days, four of these monkeys and four naïve rhesus monkeys were challenged with P. cynomolgi blood-stage parasites. B. microti persisted at low levels in all monkeys, and the clinical parameters were comparable to those of noninfected controls. There was a significant decrease in P. cynomolgi parasitemia in animals coinfected with B. microti compared to the parasitemia in animals infected with P. cynomolgi alone. This decrease in P. cynomolgi parasitemia correlated with increases in the levels of proinflammatory monocytes at the time of P. cynomolgi infection and with higher C-reactive protein (CRP) serum levels 1 week after malaria infection. Therefore, we conclude that ongoing infection with B. microti parasites leads to suppression of malaria infection.

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Section: Cd14mentioning

confidence: 99%

Suppression ofPlasmodium cynomolgiin Rhesus Macaques by Coinfection withBabesia microti

Duivenvoorde¹,

Wel²,

Werff³

et al. 2010

Infect Immun

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“…It causes high mortalities in sheep, goats, and cattle and is of major economic importance to livestock production and development in sub-Saharan Africa and on several Caribbean islands (28,36,44). Different vaccines with various efficacies have been produced against E. ruminantium, including live organisms followed by antibiotic (infection and treatment), live-attenuated vaccines, whole-organism inactivated vaccines, and recombinant protein and DNA vaccines (13,24,32,41). Although many of the vaccines have conferred at least partial protection, a continuing problem is breakthrough infection on challenge with organisms heterologous to those included in the vaccines.…”

mentioning

confidence: 99%

Diversity of Ehrlichia ruminantium Major Antigenic Protein 1-2 in Field Isolates and Infected Sheep

2009

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Proteins expressed from the map1 multigene family of Ehrlichia ruminantium are strongly recognized by immune T and B cells from infected animals or from animals that were infected and have recovered from heartwater disease (although still remaining infected carriers). Analogous multigene clusters also encode the immunodominant outer membrane proteins (OMPs) in other ehrlichial species. Recombinant protein analogs of the expressed genes and DNA vaccines based on the multigene clusters have been shown to induce protective immunity, although this was less effective in heterologous challenge situations, where the challenge strain major antigenic protein 1 (MAP1) sequence differed from the vaccine strain MAP1. Recent data for several ehrlichial species show differential expression of the OMPs in mammalian versus tick cell cultures and dominant expression of individual family members in each type of culture system. However, many genes in the clusters appear to be complete and functional and to generate mRNA transcripts. Recent data also suggest that there may be a low level of protein expression from many members of the multigene family, despite primary high-level expression from an individual member. A continuing puzzle, therefore, is the biological roles of the different members of these OMP multigene families. Complete genome sequences are now available for two geographically divergent strains of E. ruminantium (Caribbean and South Africa strains). Comparison of these sequences revealed amino acid sequence diversity in MAP1 (89% identity), which is known to confer protection in a mouse model and to be the multigene family member primarily expressed in mammalian cells. Surprisingly, however, the greatest sequence diversity (79% identity) was in the less-studied map1-2 gene. We investigated here whether this map1-2 diversity was a general feature of E. ruminantium in different cultured African strains and in organisms from infected sheep. Comparison of MAP1-2s revealed amino acid identities of 75 to 100% (mean of 86%), compared to 84 to 100% (mean of 89%) for MAP1s. Interestingly, MAP1-2s varied independently of MAP1s such that E. ruminantium strains with similar MAP1s had diverse MAP1-2s and vice versa. Different MAP1-2s were found in individual infected sheep. Different regions of a protein may be subjected to different evolutionary forces because of recombination and/or selection, which results in those regions not agreeing with a phylogeny deduced from the whole molecule. This appears to be true for both MAP1 and MAP1-2, where statistical likelihood methods detect heterogeneous evolutionary rates for segments of both molecules. Sera from infected cattle recognized a MAP1-2 variable-region peptide in enzyme-linked immunosorbent assay, but less strongly and consistently than a MAP1 peptide (MAP1B). Heterologous protective immunity may depend on recognition of a complex set of varying OMP epitopes.

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“…Since its inception about 50 years ago, attempts based on the inactivated (Martinez et al, 1996) and attenuated live vaccines (Mahan et al, 1998;Shkap et al, 2007) gave some success but not good enough to replace it. The hope for an effective and stable vaccine shifted to genomics and proteomics to deliver a non-living vaccine that can also be used in rural areas where infrastructures are limited (Mwangi et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Preparation and in vitro characterisation of Ehrlichia ruminantium plasmid DNA and proteins encapsulated into and DNA adsorbed onto biodegradable microparticles

Tshikhudo

Pretorius

Putterill

et al. 2010

Ticks and Tick-borne Diseases

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Attenuated vaccines for tropical theileriosis, babesiosis and heartwater: the continuing necessity

Cited by 82 publications

References 47 publications

Suppression ofPlasmodium cynomolgiin Rhesus Macaques by Coinfection withBabesia microti

Suppression ofPlasmodium cynomolgiin Rhesus Macaques by Coinfection withBabesia microti

Diversity of Ehrlichia ruminantium Major Antigenic Protein 1-2 in Field Isolates and Infected Sheep

Preparation and in vitro characterisation of Ehrlichia ruminantium plasmid DNA and proteins encapsulated into and DNA adsorbed onto biodegradable microparticles

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