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

Authors
  • Lyke, Kirsten E1
  • Singer, Alexandra2
  • Berry, Andrea A1
  • Reyes, Sharina2, 3
  • Chakravarty, Sumana4
  • James, Eric R4
  • Billingsley, Peter F4
  • Gunasekera, Anusha4
  • Manoj, Anita4
  • Murshedkar, Tooba4
  • Laurens, Matthew B1
  • Church, W Preston4
  • Garver Baldwin, Lindsey S5
  • Sedegah, Martha2
  • Banania, Glenna2, 3
  • Ganeshan, Harini2, 3
  • Guzman, Ivelese2, 3
  • Reyes, Anatalio2, 3
  • Wong, Mimi2, 3
  • Belmonte, Arnel2, 3
  • And 8 more
  • 1 Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • 2 Naval Medical Research Center Malaria Department, Silver Spring, Maryland, USA.
  • 3 Henry M. Jackson Foundation, Rockville, Maryland, USA.
  • 4 Sanaria Inc., Rockville, Maryland, USA.
  • 5 Pharmaceutical Systems Project Management Office US Army Medical and Material Development Activity, Fort Detrick, Maryland, USA.
  • 6 Protein Potential LLC, Rockville, Maryland, USA.
Type
Published Article
Journal
Clinical Infectious Diseases
Publisher
Oxford University Press
Publication Date
Oct 05, 2021
Volume
73
Issue
7
Identifiers
DOI: 10.1093/cid/ciaa1294
PMID: 32920641
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]

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