Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Belnoue, Elodie; Costa, Fábio Trindade Maranhão; Frankenberg, Tobias; Vigário, Ana Margarida; Voza, Tatiana; Leroy, N.; Rodrigues, Maurício M.; Landau, I.; Snounou, Georges; Rénia, Laurent

doi:10.4049/jimmunol.172.4.2487

Cited by 210 publications

(294 citation statements)

References 40 publications

(33 reference statements)

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“…Although it is reported that VACV intermediate antigens are preferentially recognized by CD4 T-cells (Yang et al, 2011b), we demonstrate that the early LACK expression driven by the early promoter of MVA-LEO160-LACK can positively influence LACK-specific CD4 T-cell responses. While antigen-specific T-cell responses can provide protective immunity against parasites (Belnoue et al, 2004), in a Leishmania infection model, only CD4 T-cell immunogenicity correlated with this protection (Darrah et al, 2007). Following Leishmania major infection, BALB/c mice show principally a Th2 response, due to the Th2 immunogenicity of the LACK antigen (Mougneau et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression

Pilato

Sánchez-Sampedro

Mejías-Pérez

et al. 2015

Journal of General Virology

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Vaccinia viruses (VACVs) with distinct early promoters have been developed to enhance antigen expression and improve antigen-specific CD8 T-cell responses. It has not been demonstrated how the length of the spacer between the coding region of the gene and its regulatory early promoter motif influences antigen expression, and whether the timing of gene expression can modify the antigen-specific CD4 T-cell response. We generated several recombinant VACVs based on the attenuated modified vaccinia Ankara (MVA) strain, which express GFP or the Leishmania LACK antigen under the control of an optimized promoter, using different spacer lengths. Longer spacer length increased GFP and LACK early expression, which correlated with an enhanced LACK-specific memory CD4 and CD8 T-cell response. These results show the importance of promoter spacer length for early antigen expression by VACV and provide alternative strategies for the design of poxvirus-based vaccines.

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Section: Discussionmentioning

confidence: 99%

Modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression

Pilato

Sánchez-Sampedro

Mejías-Pérez

et al. 2015

Journal of General Virology

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“…However, recent studies suggest an important role for non-CSP responses as well. 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).…”

Section: Discussionmentioning

confidence: 99%

“…Single immunization using CPS or late-arresting GAP approaches usually provides greater protection than an equivalent number of RAS parasites (11,26). RAS parasites arrest shortly after hepatocyte infection, whereas GAPs progress further depending on the specific genetic lesion.…”

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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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“…Efficient induction of sterile protection against malaria can be achieved in rodents by inoculation of intact sporozoites under chemoprophylaxis (Belnoue et al, 2004;Borrmann & Matuschewski, 2011). In an analogous proof-of-concept CHMI study, malaria-naïve adult volunteers received 12-15 P. falciparum-infected mosquito-bites once a month for 3 months under chloroquine prophylaxis.…”

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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Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Cited by 210 publications

References 40 publications

Modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression

Modification of promoter spacer length in vaccinia virus as a strategy to control the antigen expression

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

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