Malaria is a life-threatening disease caused by the Plasmodium parasite, which is transmitted to humans through the bite of infected mosquitoes. Despite considerable efforts to control and eradicate the disease, it remains a major global health issue, with an estimated 229 million cases and 409,000 deaths in 2019. One potential strategy for controlling malaria is through the use of whole sporozoite immunization, which involves administering live, attenuated forms of the parasite to stimulate an immune response. In a randomized trial published in BMC Medicine, researchers investigated the efficacy of whole sporozoite immunization with the Plasmodium falciparum strain NF135 in reducing the incidence of malaria in a cohort of volunteers.
A clinical trial was conducted at the Radboud University Medical Center in Nijmegen, the Netherlands, from April 2019 to February 2021. The study aimed to determine the safety and efficacy of the Pf NF135 sporozoite immunization under chemoprophylaxis.
The study population consisted of healthy adults aged 18-35 who were malaria-naïve at the time of their first immunization. Participants underwent screening for medical and family history, physical examination, complete blood counts, clinical chemistry, and serologic analysis.
Participants in cohort A received mefloquine prophylaxis three weeks prior to their first immunization. Cohort A participants were randomized to receive three immunizations, spaced one month apart, by the bites of either fifteen (high-dose) or five (low-dose) Anopheles stephensi mosquitoes infected with the C10 clone of the Pf NF135 strain. Participants underwent immunization with additional mosquitoes if insufficient infected mosquitoes had taken a blood meal.
All participants were monitored for safety data by a safety monitoring committee at specified intervals throughout the trial. Follow-up took place from day 6 until day 10 after each immunization in an outpatient setting.
The primary endpoint of the trial was the frequency and severity of adverse events after NF135 CPS immunization. Secondary endpoints included the number of sterilely protected participants and the time to parasitemia detectable by qPCR after homologous and heterologous NF54 challenge infection.
Parasite densities were quantified prospectively or retrospectively on days 6 to 10 after immunization or days 6 to 21 after challenge.
Participants in cohort B were scheduled to receive three immunizations by the bites of fifteen Pf NF135-infected An. stephensi mosquitoes and were intended to receive mefloquine prophylaxis as in cohort A.
However, due to unanticipated ongoing parasite multiplication under mefloquine prophylaxis in cohort A, and the longer observed atovaquone half-life, the study protocol was amended for cohort B to prioritize comparison of homologous (NF135) versus heterologous (NF54) efficacy over protection against two different heterologous strains.
Overall, the study aimed to assess the potential of Pf NF135 sporozoites as a viable vaccine candidate for malaria.
