A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 105 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95%CI, 35–87%) |
In this issue of AJTMH, Roestenberg and colleagues report that healthy adults can be infected by the intradermal injection of aseptic, purified, vialed, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge).1 Because of the potential of this “challenge in a bottle” to standardize and dramatically expand the use of controlled human malaria infections (CHMI) for assessment of malaria vaccines, drugs, and diagnostics, and naturally acquired immunity and innate resistance to malaria, this approach to CHMI may well turn out to be one of the major achievements in malaria vaccine research and development of the past half-century.
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Read the new paper published today in Vaccine.
Typically, vaccines distributed through the Expanded Program on Immunization (EPI) use a 2-8°C cold chain with 4-5 stops. The PfSPZ Vaccine comprises whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN(2)) vapor phase (LNVP) below -140°C and would be distributed through a LNVP cold chain. The purpose of this study was to model LNVP cold chain distribution for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare these costs to those that would be incurred in distributing a ‘conventional’ malaria vaccine through the EPI. Capital and recurrent costs |
Read the new paper published today in American Journal of Tropical Medicine and Hygiene.
Controlled human malaria infection with sporozoites is a standardized and powerful tool for evaluation of malaria vaccine and drug efficacy but so far only applied by exposure to bites of Plasmodium falciparum (Pf)-infected mosquitoes. We assessed in an open label Phase 1 trial, infection after intradermal injection of respectively 2,500, 10,000, or 25,000 aseptic, purified, vialed, cryopreserved Pf sporozoites (PfSPZ) in three groups (N = 6/group) of healthy Dutch volunteers. Infection was safe and parasitemia developed in 15 of 18 volunteers (84%), 5 of |
Read the new publication in PLOS ONE.
Plasmodium vivax (Pv) is the second most important human malaria parasite. Recent data indicate that the impact of Pv malaria on the health and economies of the developing world has been dramatically underestimated. Pv has a unique feature in its life cycle. Uninucleate sporozoites (spz), after invasion of human hepatocytes, either proceed to develop into tens of thousands of merozoites within the infected hepatocytes or remain as dormant forms called hypnozoites, which cause relapses of malaria months to several years after the primary infection. Elimination of malaria caused by Pv will |
Read the new publication in PLOS ONE.
Background
Experimental infection of malaria-naïve volunteers by the bite of Plasmodium falciparum-infected mosquitoes is a preferred means to test the protective effect of malaria vaccines and drugs. The standard model relies on the bite of five infected mosquitoes to induce malaria. We examined the efficacy of malaria transmission using mosquitoes raised aseptically in compliance with current Good Manufacturing Practices (cGMPs).
Methods and Findings
Eighteen adults aged 18–40 years were randomized to receive 1, 3 or 5 bites of Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of P. falciparum.
Seventeen |
Read the full publication in PLOS ONE.
It was recently reported that when mosquitoes infected with P. berghei sporozoites feed on mice, they deposit approximately 100–300 sporozoites in the dermis. When we inoculate P. yoelii (Py) sporozoites intravenously (IV) into BALB/c mice, the 50% infectious dose (ID50) is often less than 3 sporozoites, indicating that essentially all Py sporozoites in salivary glands are infectious. Thus, it should only take the bite of one infected mosquito to infect 100% of mice. In human subjects, it takes the bite of at least 5 P. falciparum-infected mosquitoes to achieve 100% blood |
Read the full paper as published in Human Vaccines.
Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming |
Read the full article in the Journal of Infectious Diseases.
There has been a recent call for global malaria eradication. The prospects of achieving this ambitious goal are diminished by the limited tool set now available—notably, the lack of a licensed malaria vaccine. This is in large part because the multistage Plasmodium parasites that cause malaria have a much more complex life cycle and larger genomes than do the viruses that cause smallpox and polio, the only infectious agents that have been completely or nearly eradicated from the world by vaccines. We think that (1) vaccines could play as |
