Protection against a Malaria Challenge by Sporozoite Inoculation

Roestenberg, Meta; McCall, Matthew; Hopman, Joost; Wiersma, Jorien; Luty, Adrian J. F.; Gemert, Geert Jan van; Vegte‐Bolmer, Marga van de; Schaijk, Ben van; Teelen, Karina; Arens, Theo; Spaarman, Lopke; Mast, Quirijn de; Roeffen, Will; Snounou, Georges; Rénia, Laurent; Ven, André van der; Hermsen, Cornelus C.; Sauerwein, Robert W.

doi:10.1056/nejmoa0805832

Cited by 536 publications

(647 citation statements)

References 33 publications

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“…Mouse studies suggest that fewer CPS parasites and fewer CPS immunizations are required for protection compared with the RAS regimen (26). Similarly, a single CPS immunization via the bites of 12-15 P. falciparum NF54-infected mosquitoes protected 4 of 10 human subjects from developing detectable blood-stage parasitemia following a second CPS immunization and reduced the peak parasitemia >20-fold in the remaining infected individuals (5). Although this human study was designed to test the efficacy of three CPS immunizations, relative protection from the second immunization was apparent even after the first immunization, similar to our findings here using GAP parasites.…”

Section: Discussionmentioning

confidence: 99%

“…The only vaccine approach known to induce sterile protection against challenge relies on whole organism sporozoite-stage parasites. This vaccination is experimentally achieved in mice and humans by using radiation-attenuated sporozoites (RAS) (1,2), genetically attenuated parasites (GAPs) (3), or wildtype (WT) sporozoites with chloroquine prophylaxis (CPS) (4,5). These approaches induce protective antibodies and T cells, with cytotoxic T lymphocytes (CTLs) particularly important for protection against experimental sporozoite challenge (6).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…When re-challenged after .2 years, the majority of these volunteers was still fully protected against a CHMI. Long-lasting cellular immune responses, more specifically multifunctional effector memory T-cells that produce both IFN-c and interleukin-2 upon ex vivo stimulation, are associated with protection (Roestenberg et al, 2009Teirlinck et al, 2011).…”

Section: Protection By Controlled Human Malaria Infections Under Chemmentioning

confidence: 99%

Enhancement of naturally acquired immunity against malaria by drug use

Bijker

Sauerwein

2012

Journal of Medical Microbiology

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Combination of chemoprophylaxis with chloroquine and so-called 'controlled human malaria infections' has been shown to induce sustained and fully protective immunity against malaria in experimental settings. This opens possibilities of translating this approach into an effective and applicable strategy for the field. We review the different ways in which antimalarial drugs have been used for prevention of malaria in endemic settings and discuss the possibilities and challenges of applying a strategy of drug use and naturally acquired infection in the field. IntroductionMalaria remains one of the most important infectious diseases worldwide, causing almost 655 000 deaths per year, of which the majority are children under 5 years of age. Intense malaria control interventions during the past decade have successfully established a reduction of more than 50 % in either confirmed cases of malaria or malaria admissions and deaths in 11 countries of the WHO African region (WHO, 2011a). However, increases in the number of malaria cases in 2009 in Rwanda, Sao Tome and Principe and Zambia, which previously reported reductions, illustrate the fragility of the current successes. This underlines the need for additional and innovative strategies.Availability of an effective vaccine would greatly contribute to malaria control and elimination. It is well known that clinical immunity is acquired in endemic areas after a number of years and a sufficient number of naturally acquired infections (Snow & Marsh, 1995). The search for malaria vaccines against Plasmodium falciparum has been pursued for decades, with the main focus on the development of subunit-vaccines, but with limited success. Twenty candidate vaccines are currently under clinical investigation but only one product, RTS,S, has progressed into a phase 3 field trial having recently shown encouraging indications of protection in an interim evaluation (RTS,S Clinical Trials Partnership, 2011; WHO, 2011b).One of the shortcomings of subunit-vaccines is the inability to appropriately address the significant antigenic diversity of target epitopes and the often-observed poor immunogenicity of the soluble parasite-derived proteins used. Against that background a whole-parasite approach may perform better. Indeed, immunization with sporozoite forms has consistently been shown to induce .90 % protection in rodents and humans in experimental set-ups (Friesen & Matuschewski, 2011;Hoffman et al., 2002).Transmission intensity varies greatly in sub-Saharan Africa where individuals can be subjected to up to 10 infectious bites per night at certain periods of the year. Here, we explore the idea that using medicines together with naturally acquired infection could result in the induction of protective immunity. We will review the different ways in which antimalarial drugs have been used for prevention of malaria in endemic areas and reflect on the possibilities and challenges of applying a strategy of drug use together with naturally acquired infection in the field (see Table 1 for an ov...

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“…M alaria caused by Plasmodium falciparum (''malignant malaria'') is one of the most devastating pathogens of humans (1). Plasmodium reichenowi, which infects chimpanzees and gorillas, is the closest relative of P. falciparum (2).…”

mentioning

confidence: 99%

Human-specific evolution of sialic acid targets: Explaining the malignant malaria mystery?

Varki

Gagneux

2009

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

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Protection against a Malaria Challenge by Sporozoite Inoculation

Abstract: Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.)

Cited by 536 publications

References 33 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

Enhancement of naturally acquired immunity against malaria by drug use

Human-specific evolution of sialic acid targets: Explaining the malignant malaria mystery?

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