PMID- 35928033
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220806
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 52
DP  - 2022 Oct
TI  - PfSPZ-CVac malaria vaccine demonstrates safety among malaria-experienced adults: 
      A randomized, controlled phase 1 trial.
PG  - 101579
LID - 10.1016/j.eclinm.2022.101579 [doi]
LID - 101579
AB  - BACKGROUND: Plasmodium falciparum (Pf) Sporozoite (SPZ) Chemoprophylaxis Vaccine 
      (PfSPZ-CVac) involves concurrently administering infectious PfSPZ and malaria 
      drug, often chloroquine (CQ), to kill liver-emerging parasites. PfSPZ-CVac (CQ) 
      protected 100% of malaria-naive participants against controlled human malaria 
      infection. We investigated the hypothesis that PfSPZ-CVac (CQ) is safe and 
      efficacious against seasonal, endemic Pf in malaria-exposed adults. METHODS: 
      Healthy 18-45 year olds were enrolled in a double-blind, placebo-controlled trial 
      in Bougoula-Hameau, Mali, randomized 1:1 to 2.048 x 10(5) PfSPZ (PfSPZ Challenge) 
      or normal saline administered by direct venous inoculation at 0, 4, 8 weeks. 
      Syringes were prepared by pharmacy staff using online computer-based enrolment 
      that randomized allocations. Clinical team and participant masking was assured by 
      identical appearance of vaccine and placebo. Participants received chloroquine 
      600mg before first vaccination, 10 weekly 300mg doses during vaccination, then 
      seven daily doses of artesunate 200mg before 24-week surveillance during the 
      rainy season. Safety outcomes were solicited adverse events (AEs) and related 
      unsolicited AEs within 12 days of injections, and all serious AEs. Pf infection 
      was detected by thick blood smears performed every four weeks and during febrile 
      illness over 48 weeks. Primary vaccine efficacy (VE) endpoint was time to 
      infection at 24 weeks. NCT02996695. FINDINGS: 62 participants were enrolled in 
      April/May 2017. Proportions of participants experiencing at least one solicited 
      systemic AE were similar between treatment arms: 6/31 (19.4%, 95%CI 9.2-36.3) of 
      PfSPZ-CVac recipients versus 7/31 (22.6%, 95%CI 29.2-62.2) of controls (p value = 
      1.000). Two/31 (6%) in each group reported related, unsolicited AEs. One 
      unrelated death occurred. Of 59 receiving 3 immunizations per protocol, fewer 
      vaccinees (16/29, 55.2%) became infected than controls (22/30, 73.3%). VE was 
      33.6% by hazard ratio (p = 0.21, 95%CI -27.9, 65.5) and 24.8% by risk ratio (p = 
      0.10, 95%CI -4.8, 54.3). Antibody responses to PfCSP were poor; 28% of vaccinees 
      sero-converted. INTERPRETATION: PfSPZ-CVac (CQ) was well-tolerated. The tested 
      dosing regimen failed to significantly protect against Pf infection in this very 
      high transmission setting. FUNDING: U.S. National Institutes of Health, Sanaria. 
      REGISTRATION NUMBER: ClinicalTrials.gov identifier (NCT number): NCT02996695.
CI  - (c) 2022 The Author(s).
FAU - Coulibaly, Drissa
AU  - Coulibaly D
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Kone, Abdoulaye K
AU  - Kone AK
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Traore, Karim
AU  - Traore K
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Niangaly, Amadou
AU  - Niangaly A
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Kouriba, Bourema
AU  - Kouriba B
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Arama, Charles
AU  - Arama C
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Zeguime, Amatigue
AU  - Zeguime A
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Dolo, Amagana
AU  - Dolo A
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Lyke, Kirsten E
AU  - Lyke KE
AD  - Malaria Research Program, Center for Vaccine Development and Global Health, 
      University of Maryland School of Medicine, Baltimore, Maryland, USA.
FAU - Plowe, Christopher V
AU  - Plowe CV
AD  - Malaria Research Program, Center for Vaccine Development and Global Health, 
      University of Maryland School of Medicine, Baltimore, Maryland, USA.
FAU - Abebe, Yonas
AU  - Abebe Y
AD  - Sanaria, Inc, Rockville, Maryland, USA.
FAU - Potter, Gail E
AU  - Potter GE
AD  - The Emmes Company, LLC, Rockville, MD, United States.
FAU - Kennedy, Jessie K
AU  - Kennedy JK
AD  - The Emmes Company, LLC, Rockville, MD, United States.
FAU - Galbiati, Shirley M
AU  - Galbiati SM
AD  - The Emmes Company, LLC, Rockville, MD, United States.
FAU - Nomicos, Effie
AU  - Nomicos E
AD  - Parasitic and International Programs Branch, Division of Microbiology and 
      Infectious Diseases, National Institute of Allergy and Infectious Diseases, U. S. 
      National Institutes of Health, Bethesda, MD, United States.
FAU - Deye, Gregory A
AU  - Deye GA
AD  - Parasitic and International Programs Branch, Division of Microbiology and 
      Infectious Diseases, National Institute of Allergy and Infectious Diseases, U. S. 
      National Institutes of Health, Bethesda, MD, United States.
FAU - Richie, Thomas L
AU  - Richie TL
AD  - Sanaria, Inc, Rockville, Maryland, USA.
FAU - James, Eric R
AU  - James ER
AD  - Sanaria, Inc, Rockville, Maryland, USA.
FAU - Kc, Natasha
AU  - Kc N
AD  - Sanaria, Inc, Rockville, Maryland, USA.
FAU - Sim, B Kim Lee
AU  - Sim BKL
AD  - Sanaria, Inc, Rockville, Maryland, USA.
FAU - Hoffman, Stephen L
AU  - Hoffman SL
AD  - Sanaria, Inc, Rockville, Maryland, USA.
FAU - Doumbo, Ogobara K
AU  - Doumbo OK
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Thera, Mahamadou A
AU  - Thera MA
AD  - Malaria Research and Training Center, University of Sciences, Techniques and 
      Technologies, Bamako, Mali.
FAU - Laurens, Matthew B
AU  - Laurens MB
AD  - Malaria Research Program, Center for Vaccine Development and Global Health, 
      University of Maryland School of Medicine, Baltimore, Maryland, USA.
CN  - DMID 15-0052 PfSPZ-CVac Study Team
LA  - eng
SI  - ClinicalTrials.gov/NCT02996695
PT  - Journal Article
DEP - 20220730
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC9343417
OTO - NOTNLM
OT  - ALT, alanine aminotransferase
OT  - CHMI, Controlled Human Malaria Infection
OT  - CQ, chloroquine
OT  - CSP, circumsporozoite protein
OT  - DOT, directly observed therapy
OT  - DVI, direct venous inoculation
OT  - ELISA, enzyme linked immunosorbent assay
OT  - HR, hazard ratio
OT  - Malaria vaccine
OT  - PCR, polymerase chain reaction
OT  - Pf, Plasmodium falciparum
OT  - PfSPZ Vaccine
OT  - PfSPZ-CVac
OT  - PfSPZ-CVac, Plasmodium falciparum Sporozoite Chemoprophylaxis Vaccine
OT  - Plasmodium falciparum
OT  - SMC, safety monitoring committee
OT  - SPZ, sporozoite
OT  - Sporozoite
OT  - TBS, thick blood smear
OT  - VE, vaccine efficacy
COIS- TLR, YA, BKLS, ERJ, NKC and SLH are salaried, full-time employees of Sanaria, the 
      developer and sponsor of Sanaria PfSPZ Vaccine. SLH and BKLS also have financial 
      interests in Sanaria. BKLS, and SLH are inventors on patents and applications for 
      patent that have been assigned to Sanaria. DC, AKK, KT, AN, BK, CA, AZ, AD, MAT 
      are employees of MRTC and were paid for the implementation of the study through 
      the sub contract HHSN2722013000221/HHSN27200015-10018602. MBL was supported by 
      the NIH HHSN272201300022I contract. EN participated in the study as the NIH/DMID 
      Clinical Project Manager and helped coordinate and organize DSMB meetings and 
      communications. SMG became a Novavax Inc employee after contributing to this 
      manuscript. All other authors declare no competing interests.
EDAT- 2022/08/06 06:00
MHDA- 2022/08/06 06:01
PMCR- 2022/07/30
CRDT- 2022/08/05 02:04
PHST- 2022/04/10 00:00 [received]
PHST- 2022/07/05 00:00 [revised]
PHST- 2022/07/06 00:00 [accepted]
PHST- 2022/08/05 02:04 [entrez]
PHST- 2022/08/06 06:00 [pubmed]
PHST- 2022/08/06 06:01 [medline]
PHST- 2022/07/30 00:00 [pmc-release]
AID - S2589-5370(22)00309-1 [pii]
AID - 101579 [pii]
AID - 10.1016/j.eclinm.2022.101579 [doi]
PST - epublish
SO  - EClinicalMedicine. 2022 Jul 30;52:101579. doi: 10.1016/j.eclinm.2022.101579. 
      eCollection 2022 Oct.