title: Immunogenicity and protection from malaria infection in BK-SE36 vaccinated volunteers in Uganda is not influenced by HLA-DRB1 alleles.
abstract: SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Designated as BK-SE36, the SE36 antigen was formulated with aluminum hydroxyl gel (AHG) and produced under Good Manufacturing Practice (GMP) constraints. In a Phase Ib clinical trial and follow-up study in Uganda, the risk for malaria symptoms was reduced by 72% compared with the control group. Although promising, the number of responders to the vaccine in 6-20years-olds was approximately 30% with the majority in the younger cohort. This is in contrast to the phase Ia clinical trial where response to the vaccine was 100% in Japanese malaria naive adults. A consideration that can be of importance is the involvement of host genetic factors that may influence the ability to mount an effective immune response to vaccination as well as susceptibility to malaria infection. We, therefore, analyzed allelic polymorphism of human leukocyte antigen (HLA)-DRB1 alleles using sequence-based typing (SBT). In this study, DRB1 alleles did not influence antibody response to BK-SE36 and the vaccinees susceptibility to clinical malaria.
authors.affiliation: Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: ttougan@biken.osaka-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tougan
authors.affiliation: Department of Public Health, Faculty of Medicine, Osaka City University, Osaka 545-8585, Japan; Sumida Hospital, Medical Co. Living Together Association (LTA) Clinical Pharmacology Center, Tokyo 130-0021, Japan. Electronic address: ito.kazuya@med.osaka-cu.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: nirian@biken.osaka-u.ac.jp.
authors.forename: Nirianne Marie Q
authors.initials: NM
authors.lastname: Palacpac
authors.affiliation: Med Biotech Laboratories, Plot 4-6 Bell Close, Port Bell Road Luzira, Kampala, Uganda. Electronic address: tgegwang@gmail.com.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Egwang
authors.affiliation: Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: horii@biken.osaka-u.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D014454:Uganda; D014611:Vaccination; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D059811:HLA-DRB1 Chains; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C480167:serine repeat antigen 5, Plasmodium falciparum
keywords: BK-SE36; Clinical malaria; HLA-DRB1; Immune tolerance; Malaria vaccine