期刊
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2022.1058081
关键词
BK-SE36 malaria vaccine; Plasmodium falciparum; serine repeat antigen 5; polymorphism; clinical trial
资金
- Global Health Innovative Technology Fund
- MEXT KAKENHI [GHIT 2013-105, G2014-109, G2016-106, G2019-208]
- Funds for Integrated Promotion of Social System Reform and Research and Development [15651988, 24249024]
- Grant for Translational Research Network Program [38201103-01]
- Grant for Clinical Application of Innovative Medical Seeds (AMED) [JP20lm0203135]
- Support Program for Orphan Drug Prior to the Designation (AMED)
- Irish Aid [17nk0101206j0003]
Sequence analysis of strains from Africa showed that polymorphisms in the sera5 gene were mainly confined to repeat regions, which could compromise the efficacy of the BK-SE36 vaccine. However, there was no significant difference in the haplotype diversity of sera5 between vaccinated and control participants, indicating that BK-SE36 does not elicit an allele-specific immune response.
BK-SE36, based on Plasmodium falciparum serine repeat antigen 5 (SERA5), is a blood-stage malaria vaccine candidate currently being evaluated in clinical trials. Phase 1 trials in Uganda and Burkina Faso have demonstrated promising safety and immunogenicity profiles. However, the genetic diversity of sera5 in Africa and the role of allele/variant-specific immunity remain a major concern. Here, sequence analyses were done on 226 strains collected from the two clinical trial/follow-up studies and 88 strains from two cross-sectional studies in Africa. Compared to other highly polymorphic vaccine candidate antigens, polymorphisms in sera5 were largely confined to the repeat regions of the gene. Results also confirmed a SERA5 consensus sequence with African-specific polymorphisms. Mismatches with the vaccine-type SE36 (BK-SE36) in the octamer repeat, serine repeat, and flanking regions, and single-nucleotide polymorphisms in non-repeat regions could compromise vaccine response and efficacy. However, the haplotype diversity of SERA5 was similar between vaccinated and control participants. There was no marked bias or difference in the patterns of distribution of the SE36 haplotype and no statistically significant genetic differentiation among parasites infecting BK-SE36 vaccinees and controls. Results indicate that BK-SE36 does not elicit an allele-specific immune response.
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