Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge.

BACKGROUND: Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication. METHODS: We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults. The primary end points were safety and reactogenicity. The secondary end points were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection. RESULTS: Participants were enrolled into 4 groups receiving rCSP/GLA-LSQ: 10 µg × 3 (n = 20), 30 µg × 3 (n = 10), 60 µg × 3 (n = 10), or 60 µg × 2 (n = 9); 10 participants received 30 µg rCSP alone × 3, and there were 6 infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks. CONCLUSIONS: rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess whether adjuvant or schedule adjustments improve efficacy. CLINICAL TRIALS REGISTRATION: NCT03589794.

Malaria prevention in children: an update.

PURPOSE OF REVIEW: Malaria cases and deaths decreased from 2000 to 2015 but remain increased since 2019. Several new developments and strategies could help reverse this trend. The purpose of this review is to discuss new World Health Organization (WHO) guidelines and recent research on malaria prevention in children. RECENT FINDINGS: Fifteen countries have now rolled out seasonal malaria chemoprophylaxis (SMC) in children at highest risk for severe malaria, and new WHO recommendations provide more flexibility for SMC implementation in terms of target age groups, geographic region, and number of cycles. Recent studies confirm that malaria burden in school aged children, and their contribution to transmission, is high. New guidelines permit expanded chemoprevention options for these children. Two vaccines have been approved for use in malaria endemic countries, RTS,S/AS01 E and R21/Matrix-M. Additionally, pyrethroid-chlorfenapyr bed nets are being deployed to combat resistant mosquitoes. SUMMARY: While challenges remain in malaria control towards elimination, new guidelines and recently approved vaccines offer hope. Monitoring for continued vaccine and chemoprevention effectiveness, and for possible epidemiologic shifts in severe malaria presentation and deaths as additional prevention efforts roll out will be paramount.