Pre-clinical evaluation of a whole-parasite vaccine to control human babesiosis

Cell Host Microbe. 2021 Jun 9;29(6):894-903.e5. doi: 10.1016/j.chom.2021.04.008. Epub 2021 May 13.

Abstract

Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4+ T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species.

Keywords: B. divergens; B. microti; Babesia; T cells; heterologous protection; immunity; vaccine; whole parasite vaccine.

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • B-Lymphocytes / immunology
  • Babesia microti / immunology*
  • Babesiosis / immunology*
  • Babesiosis / parasitology
  • Babesiosis / prevention & control*
  • Drug Delivery Systems / methods
  • Drug Evaluation, Preclinical*
  • Female
  • Humans
  • Immunity
  • Liposomes / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Parasitemia / immunology*
  • Parasitemia / therapy
  • T-Lymphocytopenia, Idiopathic CD4-Positive / immunology
  • Ticks / parasitology
  • Vaccines, Attenuated / immunology*
  • Vaccines, Attenuated / therapeutic use*

Substances

  • Antibodies, Protozoan
  • Liposomes
  • Vaccines, Attenuated