PD-1 deficiency enhances humoral immunity of malaria infection treatment vaccine

Infect Immun. 2015 May;83(5):2011-7. doi: 10.1128/IAI.02621-14. Epub 2015 Mar 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Protozoan / blood*
  • B-Lymphocytes / immunology
  • Cell Proliferation
  • Immunoglobulin G / blood
  • Malaria / therapy*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Mice, Inbred BALB C
  • Programmed Cell Death 1 Receptor / deficiency*
  • Spleen / immunology
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor