Malaria Transmission-Blocking Pfs25-Pfs25 Conjugate Vaccine
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Antibody
研究概览
简要总结
Background:
- Malaria, a disease transmitted by mosquitoes, affects millions of people with the highest frequency, morbidity, and mortality in infants and young children. Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host- and stage-specific proteins that can induce immunity to the disease.
- Vaccines against stages that infect mosquitoes will prevent the spread of malaria. Researchers have developed a vaccine composed of a single protein, Pfs25, to induce antibodies in the human host that will be ingested by the mosquito and prevent the malaria parasite from reproducing and stop transmission of the disease. Because Pfs25 is present only in the mosquito, humans do not develop antibodies to this antigen even in endemic areas. Repeated injections of this vaccine may be necessary.
Objectives:
- To establish the safety and optimal dosage of a malaria vaccine developed with the Pfs25 protein.
Eligibility:
- Healthy adults between 18 and 49 years of age who have never had malaria or received a malaria vaccine.
Design:
- Two doses of Pfs25 conjugate (10 micrograms and 25 micrograms) will be evaluated in this study. Participants will receive only one of these doses in order to provide the best scientific data for evaluation.
- To determine eligibility, participants will provide a medical history and have a physical examination, and will provide blood and urine samples to test for HIV/AIDS, hepatitis, and other conditions that would prevent them from participating.
- Eligible participants will receive one injection of the vaccine. The injection will be followed 30 minutes later with a temperature reading and an inspection of the vaccine site.
- Upon leaving the clinic, participants will receive diary forms, a digital thermometer, a ruler, and instructions about how to take their temperature and to measure redness and swelling (if any) at the injection site. About 6 hours later, and daily for 3 days, participants will take their temperature at home and examine the injection site. Participants will be examined at the clinic at 48 to 72 hours and on day 7 after an injection. A blood sample will be taken 1 week after immunization. - Participants will receive a second and third injection of the same vaccine at 6-week intervals, and will follow the same recording procedure given above. Further blood samples will be taken at regular intervals for up to 12 months after the vaccination, as directed by the study researchers.
详细描述
Malaria is a disease affecting millions of people in Africa, Asia, Central and South America . It has its highest frequency, morbidity, and mortality in infants and young children. For many reasons, a vaccine that would prevent this disease is sought.
Plasmodium falciparum and Plasmodium vivax, the most common and severe forms of malaria, have host and stage specific proteins that can induce immunity to disease caused by this pathogen. Surprisingly, vaccines against stages that infect mosquitos will prevent the spread of malaria (transmission-blocking). We have developed a vaccine composed of a single protein, denoted as Pfs25, to induce transmission-blocking antibodies in the human host. These transmission-blocking antibodies will be ingested by the mosquito and inactivate the sexual forms of the plasmodia (ookinetes) as they develop in the midgut of the mosquito. Because Pfs25 is present only in the mosquito, humans do not develop antibody to this antigen even in endemic areas. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of transmission-blocking antibodies. Theoretically, frequent boosting with this antigen, as is required for the other experimental malarial vaccines, would be necessary.
Our investigational vaccine is based upon the following:
- Pfs25 is a low molecular weight protein and a poor immunogen.
Bharti et al showed the protective action of antibodies to Pvs25 raised by intensive immunization of rabbits and mice (these regimes are not suitable for humans) to the recombinant protein. These findings have been confirmed; 2. Transmission of Plasmodia to mosquitos is mediated by their ingestion of gametocytes in the human bloodstream.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ELIGIBILITY AND EXCULUSION CRITERIA
- •Healthy adults, 18 to 49 years of age of either sex who do not have any of the following conditions will be eligible to participate:
- •A chronic or progressive disease requiring chronic medication,
- •History of surgical splenectomy or abnormal immune system,
- •History of neurological symptoms or signs, or mental illness,
- •Anaphylactic shock following administration of any vaccine or any other severe allergic reaction.,
- •Women who are pregnant or intend to become pregnant during the vaccine study,
- •Had malaria or received a malaria vaccine previously,
- •Allergy to vaccine components or to nickel and yeast,
- •Had cancer, HIV/AIDS, Hepatitis B or C, Guillain Barre Syndrome, chronic skin disease or have abnormal liver functions or blood counts.
排除标准
- 未提供
结局指标
主要结局
Antibody
次要结局
- Transmission-blocking activity