Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human …
KE Lyke, A Singer, AA Berry, S Reyes… - Clinical Infectious …, 2021 - academic.oup.com
KE Lyke, A Singer, AA Berry, S Reyes, S Chakravarty, ER James, PF Billingsley…
Clinical Infectious Diseases, 2021•academic.oup.comBackground 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 …
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 …
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 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.
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%.
Clinical Trials Registration
NCT02601716.
Oxford University Press