Acute Plasmodium knowlesi Infection in Olive Baboons (Papio anubis) Is Accompanied by High-Level of Gamma Interferon

Nyawira, Teresia; Gicheru, Michael M.; Kagasi, Esther; Ng’ang’a, Zipporah; Ozwara, Hastings

doi:10.5539/ijb.v4n2p92

Cited by 2 publications

(3 citation statements)

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“…Evaluation of human malaria vaccines requires experimental animal models that mimic malaria disease comparable to humans [35]. Baboons share similarities with humans that include a 28-day menstrual cycle, a flat discoid placenta and hormonal profiles allowing for malaria in pregnancy studies, and their large body size allowing frequent sampling for any clinical observation [36–38].…”

Section: Discussionmentioning

confidence: 99%

“…They are abundant and are not among the endangered NHPs in Kenya. Additionally, they are susceptible to experimental infection with P. knowlesi [35, 39–43] and recently we have also reported on the immunogenicity evaluation of P. falciparum TBV antigen Pfs48/45 [8]. Baboons also provide an alternate nonhuman primate model for evaluation of human vaccines under development.…”

Section: Discussionmentioning

confidence: 99%

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Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons

Kumar

Nyakundi

Kariuki

et al. 2013

Vaccine

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Plasmodium falciparum Pfs25 antigen, expressed on the surface of zygotes and ookinetes, is one of the leading targets for the development of a malaria transmission-blocking vaccine (TBV). Our laboratory has been evaluating DNA plasmid based Pfs25 vaccine in mice and non-human primates. Previously, we established that in vivo electroporation (EP) delivery is an effective method to improve the immunogenicity of DNA vaccine encoding Pfs25 in mice. In order to optimize the in vivo EP procedure and test for its efficacy in more clinically relevant larger animal models, we employed in vivo EP to evaluate the immune response and protective efficacy of Pfs25 encoding DNA vaccine in nonhuman primates (Olive baboons, Papio anubis). The results showed that at a dose of 2.5 mg DNA vaccine, antibody responses were significantly enhanced with EP as compared to without EP resulting in effective transmission blocking efficiency. Similar immunogenicity enhancing effect of EP was also observed with lower doses (0.5 mg and 1 mg) of DNA plasmids. Further, final boosting with a single dose of recombinant Pfs25 protein resulted in dramatically enhanced antibody titers and significantly increased functional transmission blocking efficiency. Our study suggests priming with DNA vaccine via EP along with protein boost regimen as an effective method to elicit potent immunogenicity of malaria DNA vaccines in nonhuman primates and provides the basis for further evaluation in human volunteers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons

Kumar

Nyakundi

Kariuki

et al. 2013

Vaccine

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“…Prior to infection, cryopreserved P. knowlesi parasites were retrieved and cultured overnight by modification of Rowe et al . method [ 15 , 20 ]. Parasitaemia levels, clinical changes and haematological profiles were monitored throughout the experimental period.…”

Section: Methodsmentioning

confidence: 99%

Parasite accumulation in placenta of non-immune baboons during Plasmodium knowlesi infection

Onditi

Onkoba

Omwandho

et al. 2015

Malar J

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BackgroundPlacental malaria (PM) causes adverse pregnancy outcomes in the mother and her foetus. It is difficult to study PM directly in humans due to ethical challenges. This study set out to bridge this gap by determining the outcome of PM in non-immune baboons in order to develop a non-human primate model for the disease.MethodsTen pregnant baboons were acquired late in their third trimester (day 150) and randomly grouped as seven infected and three non-infected. Another group of four nulligravidae (non-pregnant) infected was also included in the analysis of clinical outcome. Malaria infection was intravenously initiated by Plasmodium knowlesi blood-stage parasites through the femoral vein on 160th day of gestation (for pregnant baboons). Peripheral smear, placental smear, haematological samples, and histological samples were collected during the study period. Median values of clinical and haematological changes were analysed using Kruskal-Wallis and Dunn’s Multiple Comparison Test. Parasitaemia profiles were analysed using Mann Whitney U test. A Spearman’s rank correlation was run to determine the relationship between the different variables of severity scores. Probability values of P <0.05 were considered significant.ResultsLevels of white blood cells increased significantly in pregnant infected (34%) than in nulligravidae infected baboons (8%). Placental parasitaemia levels was on average 19-fold higher than peripheral parasitaemia in the same animal. Infiltration of parasitized erythrocytes and inflammatory cells were also observed in baboon placenta. Malaria parasite score increased with increase in total placental damage score (rs = 0.7650, P <0.05) and inflammatory score (rs = 0.8590, P <0.05). Although the sample size was small, absence of parasitized erythrocytes in cord blood and foetal placental region suggested lack of congenital malaria in non-immune baboons.ConclusionThis study has demonstrated accumulation of parasitized red blood cells and infiltration of inflammatory cells in the placental intravillous space (IVS) of baboons that are non-immune to malaria. This is a key feature of placental falciparum malaria in humans. This presents the baboon as a new model for the characterization of malaria during pregnancy.

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Acute Plasmodium knowlesi Infection in Olive Baboons (Papio anubis) Is Accompanied by High-Level of Gamma Interferon

Cited by 2 publications

References 3 publications

Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons

Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons

Parasite accumulation in placenta of non-immune baboons during Plasmodium knowlesi infection

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