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

Frontiers in Immunology

Immunology

Ken J. Ishii¹  Simon Cousens²  Toshihiro Horii³  Nirianne Marie Q. Palacpac³  Flavia D’Alessio⁴  Sophie Houard⁴  Odile Leroy⁴  Alphonse Ouédraogo⁵  Amidou Z. Ouedraogo⁵  Denise Hien⁵  Amidou Diarra⁵  Issiaka Soulama⁵  Issa Nebie⁵  Edith Christiane Bougouma⁵  Sodiomon B. Sirima⁵  Amadou T. Konaté⁵  Jean Sawadogo⁵  Alfred B. Tiono⁵  Gloria D. Berges⁶  Seni Kouanda⁷  Akira Myoui⁸  Sachiko Ezoe⁹  Takanobu Sato^1,10 

[1] Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan;Laboratory of Vaccine Science, Immunology Frontier Research Center, Osaka University, Suita, Japan;Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), London, United Kingdom;Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Suita, Japan;European Vaccine Initiative (EVI), Universitäts Klinikum Heidelberg, Heidelberg, Germany;Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso;Hôpital Protestant Schiphra, Ouagadougou, Burkina Faso;Institut de Recherche en Sciences de la Santé, Ouagadougou, Burkina Faso;Medical Center for Translational Research, Osaka University Hospital, Suita, Japan;Medical Center for Translational Research, Osaka University Hospital, Suita, Japan;Department of Space Infection Control, Graduate School of Medicine, Division of Health Sciences, Osaka University, Osaka, Japan;Research and Development Division, Nobelpharma Co., Ltd., Tokyo, Japan;

关键词: BK-SE36/CpG;    malaria vaccine;    Plasmodium falciparum;    serine repeat antigen;    SERA5;    safety;    immunogenicity;   

DOI  :  10.3389/fimmu.2023.1267372

 received in 2023-07-26, accepted in 2023-09-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundBK-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.MethodsA 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.ResultsOne 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.ConclusionBK-SE36/CpG was well-tolerated and immunogenic. These results pave the way for further proof-of-concept studies to demonstrate vaccine efficacy.Clinical trial registrationhttps://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1921, PACTR201701001921166.

【 授权许可】

Unknown   
Copyright © 2023 Ouédraogo, Bougouma, Palacpac, Houard, Nebie, Sawadogo, Berges, Soulama, Diarra, Hien, Ouedraogo, Konaté, Kouanda, Myoui, Ezoe, Ishii, Sato, D’Alessio, Leroy, Tiono, Cousens, Horii and Sirima