Inhibitory Activity against Plasmodium Vivax Sporozoites Induced by Plasma from Saimiri Monkeys Immunized with Circumsporozoite Recombinant Proteins or Irradiated Sporozoites

Millet, Pascal; We, Collins; Broderson,; Bathurst, Ian C.; Eh, Nardin; Rs, Nussenzweig

doi:10.4269/ajtmh.1991.45.44

Cited by 10 publications

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“…An examination of preand post-immunization sera from these monkeys in regard to the ability to inhibit sporozoite invasion of liver cell hepatocytes in vitro indicated a strong correlation with serologic response. 20 However, no relationship between the peripheral blood mononuclear cell (PBMC) responses and protection was found. 21 Additionally, there were no differences in renal pathology between vaccinated and unvaccinated controls.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Salvador I Strain of Plasmodium vivax in Non-human Primates and Anopheline Mosquitoes

Collins¹,

Sullivan²,

Strobert³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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A review is presented on studies conducted in New World monkeys and chimpanzees with the Salvador I strain of Plasmodium vivax. This isolate has been adapted to Aotus and Saimiri (squirrel) monkeys and developed as a model for the testing of antimalarial vaccines. After the injection of 10,000 sporozoites, the median prepatent period in S. boliviensis monkeys was 21.5 days. In 103 sporozoite-induced infections in splenectomized monkeys, the median maximum parasite count ranged from 2,139 to 202,368/microL, with a median maximum parasite count of 48,174/microL. Median maximum parasite counts in Aotus lemurinus griseimembra, A. nancymaae, A. azarae boliviensis, and A. vociferans monkeys were 19,902, 18,390, 21,420, and 18,210/microL, respectively and ranged from 124 to 156,000/microL. Mosquito infections were readily obtained in different species of Anopheles mosquitoes. The S. boliviensis monkey and Salvador I strain seems suitable for the testing of sporozoite and liver stage vaccines but not for blood-stage vaccines against P. vivax unless adapted further in spleen-intact Saimiri boliviensis monkeys.

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Section: Introductionmentioning

confidence: 99%

Studies on the Salvador I Strain of Plasmodium vivax in Non-human Primates and Anopheline Mosquitoes

Collins¹,

Sullivan²,

Strobert³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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“…The testing of vaccines against P. vivax has used S. boliviensis because of their susceptibility to sporozoite and trophozoite infection with Salvador I and certain other strains of P. vivax. [3][4][5][6][7][8][9][10] However, the percentage infection with sporozoites via bite has been low, and it has been necessary to intravenously inject relatively large numbers of sporozoites harvested from the salivary glands of infected mosquitoes to induce predictable infection in these monkeys. Plasmodium simium, having undergone natural adaptation in New World monkeys, is therefore being studied as a second model for the testing of antisporozoite, transmission-blocking, and bloodstage vaccines against P. vivax.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium Simium and Saimiri Boliviensis as a Model System for Testing Candidate Vaccines Against Plasmodium Vivax

Collins

Sullivan

Galland

et al. 2005

The American Journal of Tropical Medicine and Hygiene

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Observations on Plasmodium simium infections in Saimiri boliviensis boliviensis monkeys suggest that this host-parasite combination would be a suitable model for the testing of candidate vaccines against Plasmodium vivax. To evaluate the normal course of infections, parasitemia in 52 splenectomized S. boliviensis boliviensis monkeys infected with P. simium were analyzed. The mean maximum parasite count for 31 monkeys after injection with trophozoite-infected erythrocytes was 77,580/microL. Twenty-one monkeys were infected via sporozoites, and prepatent periods ranged from 14 to 24 days with a median of 15 days. The mean maximum parasite count was 29,234/microL. The mean maximum parasite count for monkeys previously infected with Old World P. vivax was 26,337/microL versus 56,362/microL for those previously infected with New World P. vivax, possibly suggesting a closer antigenic relationship between P. simium and the Old World parasites.

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“…The most-characterized antigen and one of the few vaccine candidates for P. vivax tested in clinical trials is the circumsporozoite protein (CSP). CSP is an attractive target, since anti-CSP antibodies derived from naturally infected patients or from volunteers exposed to irradiated sporozoites have the ability to inhibit the infection of hepatic cells by sporozoites in vitro (6). Unlike P. falciparum, this protein is expressed in the course of the P. vivax exoerythrocytic stage development (7) and is also expressed by hypnozoites (8).…”

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Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

et al. 2015

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dPlasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside subSaharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimeric Plasmodium yoelii proteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimeric protein based on the P. vivax CSP (PvCSP). In this engineered protein, regions of the PvCSP predicted to contain human T cell epitopes were genetically fused to an immunodominant B cell epitope derived from the N-terminal region I and to repeat sequences representing the two types of PvCSP repeats. The chimeric protein was expressed in soluble form with high yield. As the immune response to PvCSP has been reported to be genetically restricted in the murine model, we tested the immunogenicity of PvRMC-CSP in groups of six inbred strains of mice. PvRMC-CSP was able to induce robust antibody responses in all the mouse strains tested. Synthetic peptides representing the allelic forms of the P. vivax CSP were also recognized to a similar extent regardless of the mouse strain. Furthermore, the immunization regimen induced high frequencies of multifunctional CD4؉ and CD8 ؉ PvRMC-CSP-specific T cells. The depth and breadth of the immune responses elicited suggest that immunization with PvRMC-CSP can circumvent the genetic restriction of the immune response to P. vivax CSP. Interestingly, PvRMC-CSP was also recognized by naturally acquired antibodies from individuals living in areas where malaria is endemic. These features make PvRMC-CSP a promising vaccine candidate for further development. P lasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside sub-Saharan Africa, with an estimated 2.48 billion people living in areas with risk of malaria transmission (1-4). Unlike Plasmodium falciparum, P. vivax is able to persist in a latent stage called hypnozoite within infected parenchymal liver cells. Activation of hypnozoites weeks or months after the primary infection leads to new blood stage infections, causing relapses and opportunities for further transmission (5).A vaccine targeting the P. vivax preerythrocytic stages preventing the entry of sporozoites into hepatocytes or inhibiting the liver stage development could block the production of hypnozoites. The most-characterized antigen and one of the few vaccine candidates for P. vivax tested in clinical trials is the circumsporozoite protein (CSP). CSP is an attractive target, since anti-CSP antibodies derived from naturally infected patients or from volunteers exposed to irradiated sporozoites have the ability to inhibit the infection of hepatic cells by sporozoites in vitro (6). Unlike P. ...

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Inhibitory Activity against Plasmodium Vivax Sporozoites Induced by Plasma from Saimiri Monkeys Immunized with Circumsporozoite Recombinant Proteins or Irradiated Sporozoites

Cited by 10 publications

References 0 publications

Studies on the Salvador I Strain of Plasmodium vivax in Non-human Primates and Anopheline Mosquitoes

Studies on the Salvador I Strain of Plasmodium vivax in Non-human Primates and Anopheline Mosquitoes

Plasmodium Simium and Saimiri Boliviensis as a Model System for Testing Candidate Vaccines Against Plasmodium Vivax

Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

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