The deliberate infection of human participants
Published: FOBB MML JLC MEFC.
The deliberate infection of human participants with microorganisms (challenge studies) have contributed uniquely to our understanding of the pathogenesis, immune responses, treatment and prevention of numerous microbial diseases. [1] Plasmodiumfalciparum malaria is a microbe particularly suited to challenge studies as it has a relatively short and predictable asymptomatic period, a well-established diagnostic laboratory test (thick film microscopy), and no known long-term sequelae or infectious state following appropriate treatment. Studies involving controlled human malaria infection (CHMI) have become established as aOptimising CHMI Using Needle Syringekey tool to assess the efficacy of malaria vaccine and drug candidates, allowing unprecedented detailed evaluation of parasite growth and immunological responses. [2] Since the late 1980s, the number of institutions performing CHMI studies with P. falciparum has been growing and a total of 1,343 participants were experimentally infected with P. falciparum between 1985 and 2009. [3] With an increasing number of candidate malaria vaccines being developed, the number of DprE1-IN-2 centres conducting CHMI is set to expand to increase the testing capacity worldwide. The majority of CHMI trials to date have been performed using the NF54 stain of P. falciparum [4,5] or 3D7 (which is a clone of NF54) [6] sporozoites delivered by mosquito bite. [2] Standardisation of this method over the last 20 years has established a ?protocol that reliably infects 100 of malaria-naive individuals 18204824 with rare exceptions, providing a stringent, widely accepted in vivo efficacy assessment of novel drugs and vaccines. [2] Whilst the model has the benefit of mimicking the natural route of infection, it is limited by the inability to predefine and control the number of sporozoites inoculated, meaning this number can vary by several thousand sporozoites. [7?1] Mosquito bite CHMI studies can only be performed in centres with access to an appropriate insectary and entomology staff. This restriction considerably limits the number of sites that can perform such studies and has provided a major obstacle to the conduct of CHMI trials in malaria endemic regions. In principle, the most accurate and practical way of dosing sporozoites is to inject directly by needle and syringe. [2] As well as the practical advantages of ease of administration and ability to `challenge’ participants over an extended period NHS-Biotin site rather than the same day, this method would reduce variation in infectious dose between parallel clinical trials at multiple sites or sequential clinical trials at the same site. Sanaria Inc. is a biotechnology company that has developed infectious, aseptic, purified, cryopreserved P. falciparum sporozoites (NF54), which can be administered by needle and syringe. [12] The salivary glands of aseptic A. stephensi mosquitoes infected with P. falciparum sporozoites are removed by dissection and triturated to release the sporozoites which are purified, counted and cryopreserved at a specified concentration to produce the challenge inoculum; PfSPZ Challenge. The first CHMI trial using PfSPZ Challenge was performed in 2010. [12] In this dose escalation study, three doses of PfSPZ Challenge (2,500, 10,000 and 25,000 sporozoites) administered intradermally (ID) each successfully infected only 5 out of 6 injected participants (83 ). If PfSPZ Challenge is to provide an alternative to the mosquito bite CHMI, an admi.The deliberate infection of human participants
Published: FOBB MML JLC MEFC.
The deliberate infection of human participants with microorganisms (challenge studies) have contributed uniquely to our understanding of the pathogenesis, immune responses, treatment and prevention of numerous microbial diseases. [1] Plasmodiumfalciparum malaria is a microbe particularly suited to challenge studies as it has a relatively short and predictable asymptomatic period, a well-established diagnostic laboratory test (thick film microscopy), and no known long-term sequelae or infectious state following appropriate treatment. Studies involving controlled human malaria infection (CHMI) have become established as aOptimising CHMI Using Needle Syringekey tool to assess the efficacy of malaria vaccine and drug candidates, allowing unprecedented detailed evaluation of parasite growth and immunological responses. [2] Since the late 1980s, the number of institutions performing CHMI studies with P. falciparum has been growing and a total of 1,343 participants were experimentally infected with P. falciparum between 1985 and 2009. [3] With an increasing number of candidate malaria vaccines being developed, the number of centres conducting CHMI is set to expand to increase the testing capacity worldwide. The majority of CHMI trials to date have been performed using the NF54 stain of P. falciparum [4,5] or 3D7 (which is a clone of NF54) [6] sporozoites delivered by mosquito bite. [2] Standardisation of this method over the last 20 years has established a ?protocol that reliably infects 100 of malaria-naive individuals 18204824 with rare exceptions, providing a stringent, widely accepted in vivo efficacy assessment of novel drugs and vaccines. [2] Whilst the model has the benefit of mimicking the natural route of infection, it is limited by the inability to predefine and control the number of sporozoites inoculated, meaning this number can vary by several thousand sporozoites. [7?1] Mosquito bite CHMI studies can only be performed in centres with access to an appropriate insectary and entomology staff. This restriction considerably limits the number of sites that can perform such studies and has provided a major obstacle to the conduct of CHMI trials in malaria endemic regions. In principle, the most accurate and practical way of dosing sporozoites is to inject directly by needle and syringe. [2] As well as the practical advantages of ease of administration and ability to `challenge’ participants over an extended period rather than the same day, this method would reduce variation in infectious dose between parallel clinical trials at multiple sites or sequential clinical trials at the same site. Sanaria Inc. is a biotechnology company that has developed infectious, aseptic, purified, cryopreserved P. falciparum sporozoites (NF54), which can be administered by needle and syringe. [12] The salivary glands of aseptic A. stephensi mosquitoes infected with P. falciparum sporozoites are removed by dissection and triturated to release the sporozoites which are purified, counted and cryopreserved at a specified concentration to produce the challenge inoculum; PfSPZ Challenge. The first CHMI trial using PfSPZ Challenge was performed in 2010. [12] In this dose escalation study, three doses of PfSPZ Challenge (2,500, 10,000 and 25,000 sporozoites) administered intradermally (ID) each successfully infected only 5 out of 6 injected participants (83 ). If PfSPZ Challenge is to provide an alternative to the mosquito bite CHMI, an admi.
