Immunogenicity and safety of an Entamoeba histolytica adjuvanted protein vaccine candidate (LecA+GLA-3M-052 liposomes) in rhesus macaques

Hum Vaccin Immunother. 2024 Dec 31;20(1):2374147. doi: 10.1080/21645515.2024.2374147. Epub 2024 Aug 1.

Abstract

Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.

Keywords: Entamoeba histolytica; amebiasis; intranasal delivery; mucosal adjuvant; rhesus macaque.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Vaccine / administration & dosage
  • Administration, Intranasal*
  • Animals
  • Antibodies, Protozoan* / blood
  • Antibodies, Protozoan* / immunology
  • Antigens, Protozoan / immunology
  • B-Lymphocytes / immunology
  • Entamoeba histolytica* / immunology
  • Entamoebiasis* / immunology
  • Entamoebiasis* / prevention & control
  • Immunity, Humoral
  • Immunogenicity, Vaccine
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunologic Memory
  • Injections, Intramuscular
  • Interferon-gamma* / immunology
  • Interferon-gamma* / metabolism
  • Leukocytes, Mononuclear* / immunology
  • Liposomes* / administration & dosage
  • Liposomes* / immunology
  • Macaca mulatta*
  • Protozoan Proteins / immunology
  • Protozoan Vaccines* / administration & dosage
  • Protozoan Vaccines* / immunology

Substances

  • Liposomes
  • Protozoan Vaccines
  • Antibodies, Protozoan
  • Interferon-gamma
  • Adjuvants, Vaccine
  • Adjuvants, Immunologic
  • Immunoglobulin G
  • Immunoglobulin A
  • Antigens, Protozoan
  • Protozoan Proteins