PD-1 deficiency enhances humoral immunity of malaria infection treatment vaccine.
Malaria infection treatment vaccine (ITV) is a promising strategy to induce homologous and heterologous protective immunity against the blood stage of the parasite. However, the underlying mechanism of protection remains largely unknown. Here, we found that a malaria-specific antibody (Ab) could mediate the protective immunity of ITV-immunized mice. Interestingly, PD-1 deficiency greatly elevated the levels of both malaria-specific total IgG and subclass IgG2a and enhanced the protective efficacy of ITV-immunized mice against the blood-stage challenge. A serum adoptive-transfer assay demonstrated that the increased Ab level contributed to the enhanced protective efficacy of the immunized PD-1-deficient mice. Further study showed that PD-1 deficiency could also promote the expansion of germinal center (GC) B cells and malaria parasite-specific TFH cells in the spleens of ITV-immunized mice. These results suggest that PD-1 deficiency improves the protective efficacy of ITV-immunized mice by promoting the generation of malaria parasite-specific Ab and the expansion of GC B cells. The results of this study provide new evidence to support the negative function of PD-1 on humoral immunity and will guide the design of a more effective malaria vaccine.
Department of Pathogenic Biology, Third Military Medical University, Chongqing, People's Republic of China.
Taiping
T
Liu
Department of Pathogenic Biology, Third Military Medical University, Chongqing, People's Republic of China.
Xiao
X
Lu
Department of Pathogenic Biology, Third Military Medical University, Chongqing, People's Republic of China.
Chenghao
C
Zhao
Institute of Immunology of PLA, Third Military Medical University, Chongqing, People's Republic of China.
Xiaolan
X
Fu
Institute of Immunology of PLA, Third Military Medical University, Chongqing, People's Republic of China zhaotingting95@163.com xuwenyue@gmail.com.
Tingting
T
Zhao
Department of Pathogenic Biology, Third Military Medical University, Chongqing, People's Republic of China zhaotingting95@163.com xuwenyue@gmail.com.
Wenyue
W
Xu
D019264:Adoptive Transfer; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D007074:Immunoglobulin G / Q000097:blood; D008288:Malaria / Q000628:therapy*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008807:Mice, Inbred BALB C; D061026:Programmed Cell Death 1 Receptor / Q000172:deficiency*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor