Journal
CLINICAL INFECTIOUS DISEASES
Volume 73, Issue 7, Pages E2424-E2435Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciaa1294
Keywords
malaria; vaccine; PfSPZ; DVI; Ty21A
Categories
Funding
- Joint Warfighter Medical Research Program of the Department of Defense [W81XWH15-C-0073]
- US government [AI1507]
Ask authors/readers for more resources
The study demonstrated that administering four stacked priming injections resulted in 40% vaccine efficacy against heterologous malaria infection, while dose escalation of PfSPZ using single-dose priming was not significantly protective. Boosting unprotected subjects improved effectiveness to 64% at 24 weeks.
Background. 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). Methods. We immunized 4 groups that each contained 15 healthy, malaria-naive adults. Group 1 received 5 doses of 4.5 x 10(5) 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 x 10(5)/doses; Group 3 receiving 18.0 x 10(5)/doses; and Group 4 receiving 27.0 x 10(5) for dose 1 and 9.0 x 10(5) 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. Results. 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). Conclusions. 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%.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available