Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum

Genton, Blaise; D’Acremont, Valérie; Lurati-Ruiz, Floriana; Verhage, Daniele; Audran, R; Hermsen, Cornelus C.; Wolters, Liselotte; Reymond, Christophe; Spertini, François; Sauerwein, Robert W.

doi:10.1016/j.vaccine.2010.07.067

Cited by 20 publications

(10 citation statements)

References 39 publications

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“…A limited number of comparisons between Phase IIa preliminary efficacy trials and Phase IIb field efficacy trials shows that results are generally in line, but more comparisons are required before definite conclusions can be drawn [2]. Another potential difference is reflected by the almost instant delivery of parasites by five infected mosquitoes, which has been considered unnatural and a stringent test for vaccine-induced immune responses [35]. However, although the frequency of infectious mosquito bites is generally lower in malaria-endemic areas, intense transmission can occur.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Clinical and Parasitological Data from Controlled Human Malaria Infection Trials

et al. 2012

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BackgroundExposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.MethodsWe reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.ResultsWe show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.ConclusionsProcedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.

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Section: Discussionmentioning

confidence: 99%

Comparison of Clinical and Parasitological Data from Controlled Human Malaria Infection Trials

et al. 2012

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“…Here, to optimize the protective immune response, we elected to use CpG-2395 and Montanide ISA 720 VG two adjuvants that bias the immune response toward Th1 and antibody production, respectively [53–55]. These two adjuvants have already been shown to be safe and effective in human clinical trials against several pathogens and therefore, could potentially be used in the formulation of a Chlamydia vaccine [56, 57]. …”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of a vaccine formulated with the Chlamydia trachomatis serovar F, native major outer membrane protein in a nonhuman primate model

Cheng

Pal

Bettahi

et al. 2011

Vaccine

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To determine the ability of a vaccine formulated with the genital Chlamydia trachomatis, serovar F, native major outer membrane protein (Ct-F-nMOMP), to induce systemic and mucosal immune responses, rhesus macaques (Macaca mulatta) were immunized three times by the intramuscular (i.m.) and subcutaneous (s.c.) routes using CpG-2395 and Montanide ISA 720 VG, as adjuvants. As controls, another group of M. mulatta was immunized with ovalbumin instead of Ct-F-nMOMP using the same formulation and routes. High levels of Chlamydia-specific IgG and IgA antibodies were detected in plasma, vaginal washes, tears, saliva, and stools from the Ct-F-nMOMP immunized animals. Also, high neutralizing antibody titers were detected in the plasma from these animals. Monkeys immunized with ovalbumin had no detectable Chlamydia-specific antibodies. Furthermore, as measured by a lymphoproliferative assay, significant Chlamydia-specific cell-mediated immune responses were detected in the peripheral blood mononuclear cells (PBMC) from the rhesus macaques vaccinated with Ct-F-nMOMP when compared with the animals immunized with ovalbumin. In addition, the levels of two Th1 cytokines, IFN-γ and TNF-α, were significantly higher in the animals immunized with Ct-F-nMOMP when compared with those from the monkeys immunized with ovalbumin. To our knowledge, this is the first time that mucosal and systemic immune responses have been investigated in a nonhuman primate model using a subunit vaccine from a human genital C. trachomatis serovar.

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“…Such testing is usually performed in small numbers of volunteers who are vaccinated and then exposed to experimental parasite challenge with either infectious sporozoites [15]–[18] or asexual blood stages to assess the vaccine capacity to prevent infection or reduce its clinical manifestations [19].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium vivax Sporozoite Challenge in Malaria-Naïve and Semi-Immune Colombian Volunteers

et al. 2014

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BackgroundSignificant progress has been recently achieved in the development of Plasmodium vivax challenge infections in humans, which are essential for vaccine and drug testing. With the goal of accelerating clinical development of malaria vaccines, the outcome of infections experimentally induced in naïve and semi-immune volunteers by infected mosquito bites was compared.MethodsSeven malaria-naïve and nine semi-immune Colombian adults (n = 16) were subjected to the bites of 2–4 P. vivax sporozoite-infected Anopheles mosquitoes. Parasitemia levels, malaria clinical manifestations, and immune responses were assessed and compared.ResultsAll volunteers developed infections as confirmed by microscopy and RT-qPCR. No significant difference in the pre-patent period (mean 12.5 and 12.8 days for malaria-naïve and malaria-exposed, respectively) was observed but naïve volunteers developed classical malaria signs and symptoms, while semi-immune volunteers displayed minor or no symptoms at the day of diagnosis. A malaria-naïve volunteer developed a transient low submicroscopic parasitemia that cured spontaneously. Infection induced an increase in specific antibody levels in both groups.ConclusionSporozoite infectious challenge was safe and reproducible in semi-immune and naïve volunteers. This model will provide information for simultaneous comparison of the protective efficacy of P. vivax vaccines in naïve and semi-immune volunteers under controlled conditions and would accelerate P. vivax vaccine development.Trial Registrationclinicaltrials.gov NCT01585077

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Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum

Cited by 20 publications

References 39 publications

Comparison of Clinical and Parasitological Data from Controlled Human Malaria Infection Trials

Comparison of Clinical and Parasitological Data from Controlled Human Malaria Infection Trials

Immunogenicity of a vaccine formulated with the Chlamydia trachomatis serovar F, native major outer membrane protein in a nonhuman primate model

Plasmodium vivax Sporozoite Challenge in Malaria-Naïve and Semi-Immune Colombian Volunteers

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