AUTHOR=Guan Hongli , Peng Jiacong , Jiang Liping , Mo Gang , Li Xiang , Peng Xiaohong 

TITLE=CD19+CD1dhiCD5hi B Cells Can Downregulate Malaria ITV Protection by IL-10 Secretion

JOURNAL=Frontiers in Public Health

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2020.00077

DOI=10.3389/fpubh.2020.00077

ISSN=2296-2565

ABSTRACT=Infection treatment vaccine (ITV) can lead to sterile protection against malaria infection in mice and humans. However, parasite breakthrough is frequently observed post-challenge. The mechanism of rapid decline of protection after last immunization is unclear. Herein, C57BL/6 mice were immunized with 103, 105, or 107 ITV thrice in a 14-day interval. Mice were challenged with 103 parasites at 1, 3 and 6 months after last immunization and the protection was checked using blood smear. The phenotypes of B cells were analyzed by fluorescence-activated cell sorting. The levels of serum cytokines were quantified using cytometric bead array. The 103 ITV vaccination group exhibited 100% protection at 1 month after last immunization, and the 105 group showed sterile protection at 3 months after last immunization. However, the 107 group showed only partial protection. Meanwhile, the protection declined to under 50.0% at 6 months after last immunization in all three groups, especially in the 107 group. The number of memory B cells (MBC) decreased along with decline in protection. However, programmed cell death protein 1 (PD-1) expressed on the MBCs did not show significant variation among the three groups. Interestingly, CD19+CD1dhiCD5hi B cells, defined as B10 cells, exhibited negative regulation with regards to protection. The CD19+CD1dhiCD5hi B cells expressed in the 103 group at 1 months and the 105 group at 3 months post-immunization was lowest compared to those in the other groups. Moreover, the serum level of interleukin 10 (IL-10) in these two groups was also significantly lower than those in the other groups. We conclude that higher immunization dose may not lead to better protection with the malaria vaccine. CD19+CD1dhiCD5hi B cells can downregulate ITV protection against malaria via IL-10 secretion. These results could facilitate the design of an effective long-lasting malaria vaccine with the aim of maintaining MBC function.