<i>Plasmodium falciparum</i>-Specific Cellular Immune Responses after Immunization with the RTS,S/AS02D Candidate Malaria Vaccine in Infants Living in an Area of High Endemicity in Mozambique

Barbosa, Arnoldo; Naniche, Denise; Aponte, John J.; Manaca, Maria Nélia; Mandomando, Inácio; Aíde, Pedro; Sacarlal, Jahit; Renom, Montse; Lafuente, Sarah; Ballou, W. Ripley; Alonso, Pedro L.

doi:10.1128/iai.00442-09

Cited by 44 publications

(48 citation statements)

References 43 publications

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“…Although in another study only a trend was seen for higher circumsporozoite protein-specific ex vivo and cultured ELISPOT IFN-␥ responses in PBMC from protected volunteers [74], a review of subsequent phase IIa trials confirmed that higher IFN-␥ ELISPOT counts were observed consistently in protected volunteers [75]. Results from phase IIb field studies have been slightly less forthcoming, but nevertheless, PBMC-cultured IFN-␥ ELISPOT responses to 1 circumsporozoite protein epitope were associated with protection in Gambian adults [69], and a trend was seen for higher CD8 ϩ IFN-␥ responses to circumsporozoite protein in protected Mozambiquan infants [76].…”

Section: Pre-erythrocytic Stagesmentioning

confidence: 74%

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

McCall

Sauerwein

2010

Journal of Leukocyte Biology

141

113

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Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage parasites has generally been ascribed to humoral responses. A number of recent studies, however, have highlighted the existence of cellular immunity against blood-stage parasites, in particular, the prominence of IFN-γ production. Here, we have undertaken to chart the contribution of this prototypical cellular cytokine to immunity against pre-erythrocytic and blood-stage parasites. We summarize the various antiparasitic effector functions that IFN-γ serves to induce, review an array of data about its protective effects, and scrutinize evidence for any deleterious, immunopathological outcome in malaria patients. We discuss the activation and contribution of different cellular sources of IFN-γ production during malaria infection and its regulation in relation to exposure. We conclude that IFN-γ forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites and identify a number of implications for rational malaria vaccine development.

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Section: Pre-erythrocytic Stagesmentioning

confidence: 74%

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

McCall

Sauerwein

2010

Journal of Leukocyte Biology

141

113

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“…42,43 Immunological analysis indicates strongly that antibodies are the likely main protective mechanism as T-cell responses induced are very modest. 44,45 Hence, this is an anti-sporozoite vaccine whereas vectored TRAP-based vaccines are anti-liver stage. We recently assessed in a pre-clinical P. berghei model in mice whether combined use of a protein-adjuvant based anti-sporozoite vaccine could add to the partial efficacy of a vectored vaccine against the liver-stage parasite.…”

Section: Towards Higher Efficacy: Combination Approachesmentioning

confidence: 99%

Prime-boost vectored malaria vaccines: Progress and prospects

Hill

Reyes-Sandoval²,

O’Hara³

et al. 2010

Human Vaccines

188

158

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“…However, it remains unclear whether CSP-specific CTLs in naïve subjects can be primed to achieve protection with existing vaccination approaches. In addition, the CSP-based RTS, S vaccine in phase 3 human trials does not trigger strong CTL responses (18,19). The partial protection (20) from RTS,S is instead associated with antibodies and CD4 + T-cell responses (21).…”

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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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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Plasmodium falciparum-Specific Cellular Immune Responses after Immunization with the RTS,S/AS02D Candidate Malaria Vaccine in Infants Living in an Area of High Endemicity in Mozambique

Cited by 44 publications

References 43 publications

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

Prime-boost vectored malaria vaccines: Progress and prospects

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

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