In vitro activity of CD4+ and CD8+ T lymphocytes from mice immunized with a synthetic malaria peptide.

Rénia, Laurent; Marussig, Myriam; Grillot, Didier; Pied, Sylviane; Corradin, Giampietro; Miltgen, F; Giudice, Giuseppe Del; Mazier, Dominique

doi:10.1073/pnas.88.18.7963

Cited by 89 publications

(69 citation statements)

References 44 publications

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“…CSP is a target of protective class I-dependent CTL responses (10)(11)(12). Depending on the mouse model, CSP can also elicit important CD4 + T-cell responses (13,14) and MHC class IIdependent IgG responses (15). In some systems, large numbers of adoptively transferred CSP-specific T-cell clones or endogenously generated CTLs can protect mice against sporozoite challenge (8,12,14,16,17).…”

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confidence: 99%

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Murphy

Kas²,

Stone³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins.

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mentioning

confidence: 99%

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Murphy

Kas²,

Stone³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…CD4+ T cells directed against a single epitope in the amino terminus of the P. yoelii CSP eliminated infected hepatocytes from culture in an interferon-g-independent manner (Renia et al 1991(Renia et al , 1993. A heat-shock-like protein on the hepatocyte surface was a target of in vitro antibody-dependent cell-mediated cytotoxic mechanisms by liver nonparenchymal cells (Renia et al 1990).…”

Section: P Ot E N T I a L M Ec H A N I Sm S Ope R At I V E Du R I Ng mentioning

confidence: 99%

Pre–erythrocytic–stage immune effector mechanisms inPlasmodiumspp. infections

Doolan

Hoffman

1997

Phil. Trans. R. Soc. Lond. B

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The potent protective immunity against malaria induced by immunization of mice and humans with radiation–attenuated Plasmodium spp. sporozoites is thought to be mediated primarily by T–cell responses directed against infected hepatocytes. This has led to considerable efforts to develop subunit vaccines that duplicate this protective immunity, but a universally effective vaccine is still not available and in vitro correlates of protective immunity have not been established. Contributing to this delay has been a lack of understanding of the mechanisms responsible for the protection. There are now data indicating that CD8+ T cells, CD4+ T cells, cytokines, and nitric oxide can all mediate the elimination of infected hepatocytes in vitro and in vivo . By dissecting the protection induced by immunization with irradiated sporozoite, DNA and synthetic peptide–adjuvant vaccines, we have demonstrated that different T–cell–dependent immune responses mediate protective immunity in the same inbred strain of mouse, depending on the method of immunization. Furthermore, the mechanism of protection induced by a single method of immunization may vary among different strains of mice. These data have important implications for the development of pre–erythrocytic–stage vaccines designed to protect a heterogeneous human population, and of assays that predict protective immunity.

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“…In addition, the passive transfer of cytotoxic CD8+ T cells which recognize the CS protein has protected mice from challenge in both the P. berghei (84) and P. yoelii (81, 100) murine malaria models. Immunization of mice with synthetic peptides from the P. yoelii CS protein induces both CD8+ and CD4+ cytotoxic T cells that specifically eliminated infected liver cells in culture (75,101). Studies of humans immunized with irradiated P. falciparum sporozoites demonstrated the presence of CD8+ and CD4+ cytotoxic T cells that specifically recognize portions of the P. falciparum CS protein (56,61).…”

Section: The Malaria Problemmentioning

confidence: 99%

Malaria vaccine development

Jones

Hoffman

1994

Clin Microbiol Rev

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The malaria parasite life cycle presents several targets for attack, but these different parts of the life cycle are susceptible to different types of host immune response. For example, the sporozoite is most sensitive to immune antibody, while liver stage parasites can be eliminated by cytotoxic T lymphocytes. Attachment of merozoites to erythrocytes, on the other hand, can be blocked by antibody. Convincing experimental evidence shows that completely protective immunity to malaria can be induced. The challenge now is to design recombinant or synthetic vaccines that induce the right types of immune responses to specific life cycle stages. This requires the identification and characterization of B- and T-lymphocyte epitopes expressed by the parasite or by parasitized host cells. These epitopes must be incorporated into a delivery system that maximizes the interaction between the vaccine epitopes and the host immune system. Many epitopes from several parts of the life cycle are already characterized; development of multivalent vaccines, that is, vaccines which contain immunogens from more than one part of the life cycle, is a promising area for research efforts.

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In vitro activity of CD4+ and CD8+ T lymphocytes from mice immunized with a synthetic malaria peptide.

Cited by 89 publications

References 44 publications

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Pre–erythrocytic–stage immune effector mechanisms inPlasmodiumspp. infections

Malaria vaccine development

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