Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155546 | PMC |
| http://dx.doi.org/10.4269/ajtmh.14-0119 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults.
EBioMedicine
October 2024
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. Electronic address:
Article Synopsis
- The PfSPZ Vaccine shows promise as a malaria vaccine, effectively providing sterile protection in both malaria-naïve and exposed adults, relying on immune responses to early liver-stage parasites.
- A study involving 21 Tanzanian adults analyzed their immune responses to the vaccine and subsequent malaria infection, revealing robust IgG and IgM reactions to specific protein targets, regardless of HIV infection status.
- The findings highlight PfMSP5 as a significant target for vaccine-induced immunity, indicating that protecting against malaria might be possible without interference from HIV, and underscoring the need for further exploration of this immunogen.
Whole-sporozoite malaria vaccines: where we are, where we are going.
EMBO Mol Med
October 2024
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal.
The malaria vaccination landscape has seen significant advancements with the recent endorsement of RTS,S/AS01 and R21/Matrix-M vaccines, which target the pre-erythrocytic stages of Plasmodium falciparum (Pf) infection. However, several challenges remain to be addressed, including the incomplete protection afforded by these vaccines, their dependence on a single Pf antigen, and the fact that they were not designed to protect against P. vivax (Pv) malaria.
View Article and Find Full Text PDFAntibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults.
J Infect
October 2024
Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Wellcome Trust Research Programme, Kilifi, Kenya.
Objectives: Acquisition of antibodies to Plasmodium falciparum variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from PfEMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.
View Article and Find Full Text PDFFull-length MSP1 is a major target of protective immunity after controlled human malaria infection.
Life Sci Alliance
August 2024
Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya
The merozoite surface protein 1 (MSP1) is the most abundant protein on the surface of the invasive merozoite stages of and has long been considered a key target of protective immunity. We used samples from a single controlled human malaria challenge study to test whether the full-length version of MSP1 (MSP1) induced antibodies that mediated Fc-IgG functional activity in five independent assays. We found that anti-MSP1 antibodies induced complement fixation via C1q, monocyte-mediated phagocytosis, neutrophil respiratory burst, and natural killer cell degranulation as well as IFNγ production.
View Article and Find Full Text PDFBreadth of Fc-mediated effector function correlates with clinical immunity following human malaria challenge.
Immunity
June 2024
Centre of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany; Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Wellcome Trust Research Programme, Kilifi, Kenya; Department of Life Sciences, Imperial College London, London, UK. Electronic address:
Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) is routinely used to evaluate, prioritize, and quantify the efficacy of malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!