Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva

Hemmink, Johanneke D.; Weir, William; MacHugh, Niall D.; Graham, Simon P.; Patel, Ekta; Paxton, Edith; Shiels, Brian; Toye, Philip G.; Morrison, W. Ivan; Pellé, Roger

doi:10.1016/j.ijpara.2016.02.007

Cited by 34 publications

(62 citation statements)

References 50 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the VNTRs used only 8 were common between the two studies, so 14 additional VNTRS were used in the current study. Interestingly we also identified two cattle infected with Kiambu V (one immunized animal and one control) and seven tick‐derived isolates that had an MLG consistent with either Serengeti‐transformed or Muguga (Hemmink et al, ). Therefore T. parva parasites with VNTR MLGs identical to components of the Muguga cocktail version of ITM were present in both field cattle and ticks at the vaccination trial site.…”

Section: Discussionmentioning

confidence: 85%

“…Marikebuni is known for the level of diversity present within the stock exemplified by size variants of the PIM antigen (Toye, Goddeeris, Iams, Musoke, & Morrison, ) and allelic variation in the “Tp” antigens that are the targets of CD8 T cell responses induced by ITM (Hemmink et al, ). Our analysis of the Marikebuni vaccine stabilate used at Nyairo farm, using PIM‐specific primers revealed two major PCR products of very different sizes, suggesting the presence of at least two PIM size variants (data not shown).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Multilocus genotyping of Theileria parva isolates associated with a live vaccination trial in Kenya provides evidence for transmission of immunizing parasites into local tick and cattle populations

Bishop

Odongo

Spooner

et al. 2020

Transbound Emerg Dis

View full text Add to dashboard Cite

The live infection and treatment (ITM) vaccination procedure using the trivalent Muguga cocktail is increasingly being used to control East Coast fever, with potential implications for Theileria parva population genetic structure in the field. Transmission of the Kiambu V T. parva component to unvaccinated cattle has previously been described in Uganda. We monitored the T. parva carrier state in vaccinated and control animals on a farm in West Kenya where an ITM stabilate derived from the Kenyan T. parva Marikebuni stock was evaluated for field efficacy. A nested PCR‐based Marikebuni‐specific marker identified a carrier state in nine of ten vaccinated animals, detectable for a period of two years. We used 22 variable number tandem repeat (VNTR) markers to determine multilocus genotypes (MLGs) of 19 T. parva schizont‐infected lymphocyte isolates derived from cattle and field ticks. Two isolates from unimmunized cattle were identical to the Marikebuni vaccination stock. Two cattle isolates were identical to a Muguga cocktail component Kiambu V. Seven isolates from ticks exhibited MLGs that were identical to the Serengeti/Muguga vaccine stocks. Six cattle and two tick‐derived stocks exhibited unique MLGs. The data strongly suggest transmission of immunizing genotypes, from Marikebuni vaccine‐induced carrier cattle to unimmunized cattle. It is possible that genotypes similar to those in the Muguga cocktail are present in the field in Western Kenya. An alternative hypothesis is that these parasites may have originated from vaccine trial sites in Eastern Uganda. If correct, this suggests that T. parva stocks used for immunization can potentially be disseminated 125 km beyond the immediate vaccination site. Regardless of their origin, the data provide evidence that genotypes similar to those in the Muguga cocktail are circulating in the field in East Africa, alleviating concerns about dissemination of ‘alien’ T. parva germplasm through live vaccination.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Multilocus genotyping of Theileria parva isolates associated with a live vaccination trial in Kenya provides evidence for transmission of immunizing parasites into local tick and cattle populations

Bishop

Odongo

Spooner

et al. 2020

Transbound Emerg Dis

View full text Add to dashboard Cite

show abstract

“…parva Muguga reference sequence (Oura et al., ). They are informative when applied to characterization of vaccine stabilates, especially when next‐generation sequencing technologies are applied to specific VNTR loci to generate high coverage data that reveal the presence of ‘minor’ alleles (Hemmink et al., ).…”

Section: Vaccine Stabilate Compositionmentioning

confidence: 99%

A review of recent research on Theileria parva : Implications for the infection and treatment vaccination method for control of East Coast fever

Bishop

Odongo

Ahmed

et al. 2020

Transbound Emerg Dis

View full text Add to dashboard Cite

The infection and treatment (ITM) live vaccination method for control of Theileria parva infection in cattle is increasingly being adopted, particularly in Maasai pastoralist systems. Several studies indicate positive impacts on human livelihoods. Importantly, the first detailed protocol for live vaccine production at scale has recently been published. However, quality control and delivery issues constrain vaccination sustainability and deployment. There is evidence that the distribution of T. parva is spreading from endemic areas in East Africa, North into Southern Sudan and West into Cameroon, probably as a result of anthropogenic movement of cattle. It has also recently been demonstrated that in Kenya, T. parva derived from cape buffalo can ‘breakthrough’ the immunity induced by ITM. However, in Tanzania, breakthrough has not been reported in areas where cattle co‐graze with buffalo. It has been confirmed that buffalo in northern Uganda national parks are not infected with T. parva and R. appendiculatus appears to be absent, raising issues regarding vector distribution. Recently, there have been multiple field population genetic studies using variable number tandem repeat (VNTR) sequences and sequencing of antigen genes encoding targets of CD8+ T‐cell responses. The VNTR markers generally reveal high levels of diversity. The antigen gene sequences present within the trivalent Muguga cocktail are relatively conserved among cattle transmissible T. parva populations. By contrast, greater genetic diversity is present in antigen genes from T. parva of buffalo origin. There is also evidence from several studies for transmission of components of stocks present within the Muguga cocktail, into field ticks and cattle following induction of a carrier state by immunization. In the short term, this may increase live vaccine effectiveness, through a more homogeneous challenge, but the long‐term consequences are unknown.

show abstract

“…However, the results of these two studies both suggested that the Serengeti isolate had at some point become contaminated with parasites from the Muguga isolate. Amplicon sequencing and satellite DNA typing also demonstrated that the vaccine components contained minor genotypic components present at <5% within the vaccine parasites . If these minor components contribute to the broad protective capacity of the vaccine, then the possibility that these components might not be present in all vaccine batches or indeed all vaccine doses is of concern regarding standardization of vaccine content.…”

Section: Live Vaccinesmentioning

confidence: 99%

“…An additional T. annulata antigen was identified by screening a small number of parasite cDNAs. Analyses of sequences of Tp9 and the orthologue in T. annulata in different parasite isolates have shown that this antigen is highly polymorphic in both parasite species and that the corresponding CD8 T‐cell lines exhibit parasite strain specificity. Although the repertoire of antigens recognized by CD8 T cells specific for these parasites is far from complete, these initial findings suggest that there is likely to be substantial commonality in the gene products that they recognize.…”

Section: Approaches To Development Of Subunit Vaccinesmentioning

confidence: 99%

Approaches to vaccination against Theileria parva and Theileria annulata

Nene

Morrison

2016

Parasite Immunology

View full text Add to dashboard Cite

SummaryDespite 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.

show abstract

Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva

Abstract: Graphical abstract

Cited by 34 publications

References 50 publications

Multilocus genotyping of Theileria parva isolates associated with a live vaccination trial in Kenya provides evidence for transmission of immunizing parasites into local tick and cattle populations

Multilocus genotyping of Theileria parva isolates associated with a live vaccination trial in Kenya provides evidence for transmission of immunizing parasites into local tick and cattle populations

A review of recent research on Theileria parva : Implications for the infection and treatment vaccination method for control of East Coast fever

Approaches to vaccination against Theileria parva and Theileria annulata

Contact Info

Product

Resources

About