Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human Malaria Infection

• Published in: Clinical infectious diseases Vol. 73; no. 7; pp. e2424 - e2435
• Main Authors: Lyke, Kirsten E, Singer, Alexandra, Berry, Andrea A, Reyes, Sharina, Chakravarty, Sumana, James, Eric R, Billingsley, Peter F, Gunasekera, Anusha, Manoj, Anita, Murshedkar, Tooba, Laurens, Matthew B, Church, W Preston, Garver Baldwin, Lindsey S, Sedegah, Martha, Banania, Glenna, Ganeshan, Harini, Guzman, Ivelese, Reyes, Anatalio, Wong, Mimi, Belmonte, Arnel, Ozemoya, Amelia, Belmonte, Maria, Huang, Jun, Villasante, Eileen, Sim, B Kim Lee, Hoffman, Stephen L, Richie, Thomas L, Epstein, Judith E
• Format: Journal Article
• Language: English
• Published: United States 05.10.2021
• Subjects: Adult; Animals; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum - prevention & control; Plasmodium falciparum; Sporozoites; PfSPZ; vaccine; Ty21A; malaria; DVI
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciaa1294

A live-attenuated Plasmodium falciparum sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same P. falciparum strain as in the vaccine). Using a more stringent CHMI, with heterologous parasites (different P. falciparum strain), we assessed the impact of higher PfSPZ doses, a novel multi-dose prime regimen, and a delayed vaccine boost upon vaccine efficacy (VE). We immunized 4 groups that each contained 15 healthy, malaria-naive adults. Group 1 received 5 doses of 4.5 x 105 PfSPZ (Days 1, 3, 5, and 7; Week 16). Groups 2, 3, and 4 received 3 doses (Weeks 0, 8, and 16), with Group 2 receiving 9.0 × 105/doses; Group 3 receiving 18.0 × 105/doses; and Group 4 receiving 27.0 × 105 for dose 1 and 9.0 × 105 for doses 2 and 3. VE was assessed by heterologous CHMI after 12 or 24 weeks. Volunteers not protected at 12 weeks were boosted prior to repeat CHMI at 24 weeks. At 12-week CHMI, 6/15 (40%) participants in Group 1 (P = .04) and 3/15 (20%) participants in Group 2 remained aparasitemic, as compared to 0/8 controls. At 24-week CHMI, 3/13 (23%) participants in Group 3 and 3/14 (21%) participants in Group 4 remained aparasitemic, versus 0/8 controls (Groups 2-4, VE not significant). Postboost, 9/14 (64%) participants versus 0/8 controls remained aparasitemic (3/6 in Group 1, P = .025; 6/8 in Group 2, P = .002). Administering 4 stacked priming injections (multi-dose priming) resulted in 40% VE against heterologous CHMI, while dose escalation of PfSPZ using single-dose priming was not significantly protective. Boosting unprotected subjects improved VE at 24 weeks, to 64%. NCT02601716.