Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults

Abstract

Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. Plasmodium falciparum sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 106 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 105 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7–13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, P = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.

Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers

“…We used samples from volunteers enrolled in four studies conducted in Bagamoyo, Tanzania (acronyms BSPZV1, BSPZV2, and BSPZV3a) and on Bioko Island in Equatorial Guinea (acronym EGSPZV2) registered at Clinicaltrials.gov with registration numbers NCT03420053, NCT02132299, NCT02613520, and NCT02859350, respectively. Detailed trial designs and study procedures such as pre-de ned inclusion and exclusion criteria have been described previously [9,10,29,30]. Brie y, these trials evaluated the safety, immunogenicity and e cacy of live, cryopreserved, puri ed, whole P. falciparum sporozoites in malaria preexposed volunteers.…”

“…TBS were also performed on day 28 before malaria drug treatment. Prepatent periods were calculated from the time of PfSPZ challenge to rst positivity detected by qPCR and TBS [9,10,29,30]. Parasite multiplication rate (PMR) was assessed using a linear model tted to log10transformed qPCR data as published [44].…”

Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers

“…Serum samples for anti-PfCSP antibody evaluation were collected before vaccination (baseline) and 14 days post last vaccination. Anti-PfCSP total IgG levels were measured by enzyme linked immunosorbent assay (ELISA) as described previously [9,10,29,30].…”

“…Asexual blood-stage malaria parasitemia during CHMI was assessed using thick blood smear (TBS) microscopy and retrospectively analysed using stored whole blood samples and qPCR as described [9,10,29,30]. Whole blood samples for the assessment of parasitemia were taken before CHMI and during the observation period beginning at day 9 after parasite challenge inoculation until volunteers either became asexual blood-stage malaria positive or until day 21.…”

“…To date, the number of human viruses investigated in this context is limited and their mechanisms in modulation of vaccine-induced responses remain unclear. such as pre-defined inclusion and exclusion criteria have been described previously [9,10,29,30]. Briefly, these trials evaluated the safety, immunogenicity and efficacy of live, cryopreserved, purified, whole P. falciparum sporozoites in malaria pre-exposed volunteers.…”