Survival and antigenic profile of irradiated malarial sporozoites in infected liver cells

Suhrbier, Andreas; Winger, Larry; Castellano, Elena; Sinden, Robert E.

doi:10.1128/iai.58.9.2834-2839.1990

Cited by 42 publications

(11 citation statements)

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“…However, more recent studies carried out in parallel under in vivo and in vitro conditions have shown in both humans and rodents that protection depends on the abilities of irradiated sporozoites to penetrate hepatocytes and, further, to transform into uninucleate liver trophozoites (14). The indication that persistent liver form parasites are required to induce protection (14,38,46) was confirmed recently (34,44).…”

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confidence: 77%

Immunogenicity of FourPlasmodium falciparumPreerythrocytic Antigens inAotus lemurinusMonkeys

et al. 1998

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Aotus lemurinus monkeys were immunized with pools of either lipid-tailed peptides injected in PBS or peptides in Montanide ISA-51, all derived from four Plasmodium falciparum pre-erythrocytic antigens, namely, LSA1, LSA3, SALSA, and STARP. These formulations were well tolerated. Their immunogenicity was demonstrated by the induction of both B- and T-cell responses to most of the peptides studied (of the 12, 10 induced antibody production, 9 induced T-cell proliferative responses, and all 12 induced gamma interferon secretion). Immune responses proved to be long lasting, since some were still detectable 210 days after immunization. Of particular importance is the fact that B- and T-cell responses elicited in this way by synthetic peptides were specific for native parasite proteins on P. falciparumsporozoites and liver stage parasites.

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confidence: 77%

Immunogenicity of FourPlasmodium falciparumPreerythrocytic Antigens inAotus lemurinusMonkeys

et al. 1998

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“…Nevertheless, the partial development of intranuclear parasites in vivo may participate in the development of immune responses against Plasmodium pre‐erythrocytic stages. In this regard, the partial EEF development resulting from infection by radiation‐attenuated (Suhrbier et al ., 1990; Silvie et al ., 2002) or genetically attenuated (van Dijk et al ., 2005; Mueller et al ., 2005a,b) sporozoites is associated with the induction of protective immune responses against subsequent sporozoite challenge (Nussenzweig et al ., 1967; Hoffman et al ., 2002; van Dijk et al ., 2005; Mueller et al ., 2005a,b).…”

Section: Discussionmentioning

confidence: 99%

Expression of human CD81 differently affects host cell susceptibility to malaria sporozoites depending on the Plasmodium species

et al. 2006

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SummaryPlasmodium sporozoites can enter host cells by two distinct pathways, either through disruption of the plasma membrane followed by parasite transmigration through cells, or by formation of a parasitophorous vacuole (PV) where the parasite further differentiates into a replicative exo-erythrocytic form (EEF). We now provide evidence that following invasion without PV formation, transmigrating Plasmodium falciparum and Plasmodium yoelii sporozoites can partially develop into EEFs inside hepatocarcinoma cell nuclei. We also found that rodent P. yoelii sporozoites can infect both mouse and human hepatocytes, while human P. falciparum sporozoites infect human but not mouse hepatocytes. We have previously reported that the host tetraspanin CD81 is required for PV formation by P. falciparum and P. yoelii sporozoites. Here we show that expression of human CD81 in CD81-knockout mouse hepatocytes is sufficient to confer susceptibility to P. yoelii but not P. falciparum sporozoite infection, showing that the narrow P. falciparum host tropism does not rely on CD81 only. Also, expression of CD81 in a human hepatocarcinoma cell line is sufficient to promote the formation of a PV by P. yoelii but not P. falciparum sporozoites. These results highlight critical differences between P. yoelii and P. falciparum sporozoite infection, and suggest that in addition to CD81, other molecules are specifically required for PV formation during infection by the human malaria parasite.

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“…This development entails a sequential change in the proteins expressed, sporozoite surface proteins are progressively downregulated, liver stage specific proteins are expressed and merozoite proteins upregulated. [16][17][18][19] Schizont development takes from 3-11 days dependent upon parasite species, in which time some parasite proteins are inexplicably processed on proteasomes in the host cell cytoplasm, and presented by class I MHC on the hepatocyte surface, identifying infected cells for attack by both CD4 and CD8 T cells, and killing by cytokine mediated mechanisms. These processes remain very poorly understood, and clearly require further study if pre-erythrocytic vaccines targeting finite numbers of proteins/epitopes are to achieve their maximal potential.…”

Section: The Parasites' Life Cycles and Anti-parasitic Vaccinesmentioning

confidence: 99%

A biologist’s perspective on malaria vaccine development

Sinden¹

2010

Human Vaccines

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A vaccine to reduce human suffering caused by malarial parasites has been the holy grail of malaria research. Early studies in the 1940s indicated that attenuated parasites could induce useful immunity. Since that time the genomic revolution led inevitably to the idea of cheap production of safe recombinant vaccines using either expressed protein or DNA vector technologies. It has been difficult to reflect with these 'simple' formulations the efficacies observed with intact parasite immunogens. With the new-found ability to attenuate the parasites by genetic manipulation, ideas have come full circle. Some of the highs and lows of this journey are described from the specific viewpoint of our growing understanding of parasite biology. The objective of many current vaccine initiatives targeting morbidity and mortality is questioned in the light of renewed calls to consider eradication as an objective. The biological rational for approaches to limit parasite transmission are highlighted and their place in future efforts to improve the lives of the 40% of the world's population at risk of the disease is discussed.

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Survival and antigenic profile of irradiated malarial sporozoites in infected liver cells

Cited by 42 publications

References 42 publications

Immunogenicity of FourPlasmodium falciparumPreerythrocytic Antigens inAotus lemurinusMonkeys

Immunogenicity of FourPlasmodium falciparumPreerythrocytic Antigens inAotus lemurinusMonkeys

Expression of human CD81 differently affects host cell susceptibility to malaria sporozoites depending on the Plasmodium species

A biologist’s perspective on malaria vaccine development

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