Immune responses of mice with different genetic backgrounds to improved multiepitope, multitarget malaria vaccine candidate antigen FALVAC-1A

Clin Vaccine Immunol. 2008 Nov;15(11):1674-83. doi: 10.1128/CVI.00164-08. Epub 2008 Sep 10.

Abstract

FALVAC-1A is a second-generation multitarget, multiepitope synthetic candidate vaccine against Plasmodium falciparum, incorporating elements designed to yield a stable and immunogenic molecule. Characteristics of the immunogenicity of FALVAC-1A were evaluated in congenic (H-2(b), H-2(k), and H-2(d)) and outbred strains of mice. The influences of four adjuvants (aluminum phosphate, QS-21, Montanide ISA-720, and copolymer CRL-1005) on different aspects of the immune response were also assessed. FALVAC-1A generated strong antibody responses in all mouse strains. The highest mean enzyme-linked immunosorbent assay (ELISA) antibody concentrations against FALVAC-1A were observed in the outbred ICR mice, followed by B10.BR, B10.D2, and C57BL/6 mice, though this order varied for the different adjuvants, with no statistical differences between mouse strains. In all mouse strains, the highest anti-FALVAC-1A antibody titers in ELISAs were induced by FALVAC-1A in copolymer and ISA-720 formulations, followed by QS-21 and AlPO4. These antibodies were of all four subclasses, though immunoglobulin G1 (IgG1) predominated, with the exception of FALVAC-1A with the QS-21 adjuvant, which induced predominantly IgG2c responses. Both sporozoites and blood stages of P. falciparum were recognized by anti-FALVAC-1A sera in the immunofluorescence assay. In addition to antibody, cellular immune responses were detected; these responses were studied by examining spleen cells producing gamma interferon and interleukin-4 in enzyme-linked immunospot assays. In summary, FALVAC-1A was found to be highly immunogenic and elicited functionally relevant antibodies that can recognize sporozoites and blood-stage parasites in diverse genetic backgrounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Protozoan / blood
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / genetics
  • Epitopes / immunology*
  • Female
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lymphocytes / immunology
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Plasmodium falciparum / immunology*
  • Spleen / immunology
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes
  • Immunoglobulin G
  • Malaria Vaccines
  • Vaccines, Synthetic
  • Interleukin-4
  • Interferon-gamma