PMID- 37908361
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231106
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabe 
      adults and children: a phase 1b randomised, controlled, double-blinded, age 
      de-escalation trial.
PG  - 1267372
LID - 10.3389/fimmu.2023.1267372 [doi]
LID - 1267372
AB  - BACKGROUND: BK-SE36/CpG is a recombinant blood-stage malaria vaccine candidate 
      based on the N-terminal Plasmodium falciparum serine repeat antigen5 (SE36), 
      adsorbed to aluminium hydroxide gel and reconstituted, prior to administration, 
      with synthetic oligodeoxynucleotides bearing CpG motifs. In healthy Japanese 
      adult males, BK-SE36/CpG was well tolerated. This study assessed its safety and 
      immunogenicity in healthy malaria-exposed African adults and children. METHODS: A 
      double-blind, randomised, controlled, age de-escalating clinical trial was 
      conducted in an urban area of Ouagadougou, Burkina Faso. Healthy participants 
      (n=135) aged 21-45 years (Cohort 1), 5-10 years (Cohort 2) and 12-24 months 
      (Cohort 3) were randomised to receive three vaccine doses (Day 0, 28 and 112) of 
      BK-SE36/CpG or rabies vaccine by intramuscular injection. RESULTS: One hundred 
      thirty-four of 135 (99.2%) subjects received all three scheduled vaccine doses. 
      Vaccinations were well tolerated with no related Grade 3 (severe) adverse events 
      (AEs). Pain/limitation of limb movement, headache in adults and fever in younger 
      children (all mild to moderate in intensity) were the most frequently observed 
      local and systemic AEs. Eighty-three of BK-SE36/CpG (91%) recipients and 37 of 
      control subjects (84%) had Grade 1/2 events within 28 days post vaccination. 
      Events considered by the investigator to be vaccine related were experienced by 
      38% and 14% of subjects in BK-SE36/CpG and control arms, respectively. Throughout 
      the trial, six Grade 3 events (in 4 subjects), not related to vaccination, were 
      recorded in the BK-SE36/CpG arm: 5 events (in 3 subjects) within 28 days of 
      vaccination. All serious adverse events (SAEs) (n=5) were due to severe malaria 
      (52-226 days post vaccination) and not related to vaccination. In all cohorts, 
      BK-SE36/CpG arm had higher antibody titres after Dose 3 than after Dose 2. 
      Younger cohorts had stronger immune responses (12-24-month-old > 5-10 years-old > 
      21-45 years-old). Sera predominantly reacted to peptides that lie in 
      intrinsically unstructured regions of SE36. In the control arm, there were no 
      marked fold changes in antibody titres and participants' sera reacted poorly to 
      all peptides spanning SE36. CONCLUSION: BK-SE36/CpG was well-tolerated and 
      immunogenic. These results pave the way for further proof-of-concept studies to 
      demonstrate vaccine efficacy. CLINICAL TRIAL REGISTRATION: 
      https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1921, PACTR201701001921166.
CI  - Copyright (c) 2023 Ouedraogo, Bougouma, Palacpac, Houard, Nebie, Sawadogo, Berges, 
      Soulama, Diarra, Hien, Ouedraogo, Konate, Kouanda, Myoui, Ezoe, Ishii, Sato, 
      D'Alessio, Leroy, Tiono, Cousens, Horii and Sirima.
FAU - Ouedraogo, Alphonse
AU  - Ouedraogo A
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Bougouma, Edith Christiane
AU  - Bougouma EC
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Palacpac, Nirianne Marie Q
AU  - Palacpac NMQ
AD  - Department of Malaria Vaccine Development, Research Institute for Microbial 
      Diseases, Osaka University, Suita, Japan.
FAU - Houard, Sophie
AU  - Houard S
AD  - European Vaccine Initiative (EVI), Universitats Klinikum Heidelberg, Heidelberg, 
      Germany.
FAU - Nebie, Issa
AU  - Nebie I
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Sawadogo, Jean
AU  - Sawadogo J
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Berges, Gloria D
AU  - Berges GD
AD  - Hopital Protestant Schiphra, Ouagadougou, Burkina Faso.
FAU - Soulama, Issiaka
AU  - Soulama I
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Diarra, Amidou
AU  - Diarra A
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Hien, Denise
AU  - Hien D
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Ouedraogo, Amidou Z
AU  - Ouedraogo AZ
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Konate, Amadou T
AU  - Konate AT
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Kouanda, Seni
AU  - Kouanda S
AD  - Institut de Recherche en Sciences de la Sante, Ouagadougou, Burkina Faso.
FAU - Myoui, Akira
AU  - Myoui A
AD  - Medical Center for Translational Research, Osaka University Hospital, Suita, 
      Japan.
FAU - Ezoe, Sachiko
AU  - Ezoe S
AD  - Medical Center for Translational Research, Osaka University Hospital, Suita, 
      Japan.
AD  - Department of Space Infection Control, Graduate School of Medicine, Division of 
      Health Sciences, Osaka University, Osaka, Japan.
FAU - Ishii, Ken J
AU  - Ishii KJ
AD  - Center for Vaccine and Adjuvant Research, National Institutes of Biomedical 
      Innovation, Health and Nutrition, Ibaraki, Japan.
AD  - Laboratory of Vaccine Science, Immunology Frontier Research Center, Osaka 
      University, Suita, Japan.
AD  - Division of Vaccine Science, Department of Microbiology and Immunology, The 
      Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
FAU - Sato, Takanobu
AU  - Sato T
AD  - Research and Development Division, Nobelpharma Co., Ltd., Tokyo, Japan.
FAU - D'Alessio, Flavia
AU  - D'Alessio F
AD  - European Vaccine Initiative (EVI), Universitats Klinikum Heidelberg, Heidelberg, 
      Germany.
FAU - Leroy, Odile
AU  - Leroy O
AD  - European Vaccine Initiative (EVI), Universitats Klinikum Heidelberg, Heidelberg, 
      Germany.
FAU - Tiono, Alfred B
AU  - Tiono AB
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
FAU - Cousens, Simon
AU  - Cousens S
AD  - Department of Infectious Disease Epidemiology, London School of Hygiene and 
      Tropical Medicine (LSHTM), London, United Kingdom.
FAU - Horii, Toshihiro
AU  - Horii T
AD  - Department of Malaria Vaccine Development, Research Institute for Microbial 
      Diseases, Osaka University, Suita, Japan.
FAU - Sirima, Sodiomon B
AU  - Sirima SB
AD  - Groupe de Recherche Action en Sante (GRAS), Ouagadougou, Burkina Faso.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20231016
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Malaria Vaccines)
RN  - 0 (Peptides)
SB  - IM
MH  - Male
MH  - Humans
MH  - Adult
MH  - Child
MH  - Infant
MH  - Child, Preschool
MH  - Young Adult
MH  - Middle Aged
MH  - *Malaria Vaccines
MH  - *Malaria, Falciparum/prevention & control
MH  - *Malaria/prevention & control
MH  - Double-Blind Method
MH  - Peptides
PMC - PMC10613650
OTO - NOTNLM
OT  - BK-SE36/CpG
OT  - Plasmodium falciparum
OT  - SERA5
OT  - immunogenicity
OT  - malaria vaccine
OT  - safety
OT  - serine repeat antigen
COIS- TH is the inventor of BK-SE36; TH and KI are inventors of BK-SE36/CpG. NP and TH 
      are supported by a research fund from Nobelpharma Co., Ltd NPC, the clinical 
      trial sponsor. TS is an employee and SE is medical adviser of NPC. These 
      involvements did not influence the design of the study, the collection, analyses, 
      access to and interpretation of data, and the writing of this manuscript. The 
      remaining authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The author(s) declared that they were an editorial board 
      member of Frontiers, at the time of submission. This had no impact on the peer 
      review process and the final decision.
EDAT- 2023/11/01 06:43
MHDA- 2023/11/02 12:42
PMCR- 2023/01/01
CRDT- 2023/11/01 03:52
PHST- 2023/07/26 00:00 [received]
PHST- 2023/09/25 00:00 [accepted]
PHST- 2023/11/02 12:42 [medline]
PHST- 2023/11/01 06:43 [pubmed]
PHST- 2023/11/01 03:52 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1267372 [doi]
PST - epublish
SO  - Front Immunol. 2023 Oct 16;14:1267372. doi: 10.3389/fimmu.2023.1267372. 
      eCollection 2023.