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Vaccine Detail

PfRH5 DNA Vaccine
Vaccine Information
  • Vaccine Name: PfRH5 DNA Vaccine
  • Target Pathogen: Plasmodium spp.
  • Target Disease: Malaria
  • Type: DNA vaccine
  • Status: Research
  • Host Species for Licensed Use: None
  • Antigen: PfRH5: reticulocyte-binding protein homolog 5, a leading blood-stage antigen to APCs. The vaccine uses PfRH5ΔNL, the crystal structure and key functional antibody epitopes for the trunacated version of PfRH5. (Bjerkan et al., 2021)
  • RH5 gene engineering:
    • Type: Recombinant protein preparation
    • Description: The crystal structure and key functional antibody epitopes for the truncated version of PfRH5 were characterized to create PfRH5ΔNL, used as the vaccine antigen. (Bjerkan et al., 2021)
    • Detailed Gene Information: Click Here.
  • Preparation: DNA vaccines were encoded in a pUMVC4a plasmid vector (Aldevron) under a CMV-IE promoter and containing a tPA signal peptide. The targeted constructs were cloned into pUMVC4a using PmlI and BamHI.(Bjerkan et al., 2021)
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: The PfRH5 DNA Vaccine vaccine is designed as bivalent homodimers where each chain is composed of an amino-terminal single chain fragment variable (scFv) targeting unit specific for major histocompatibility complex class II (MHCII) expressed on APCs, and a carboxyl-terminal antigenic unit genetically linked by the dimerization units. This vaccine uses PfRH5ΔNL as the antigen, with the APC-targeted vaccine construct, termed a “Vaccibody”. (Bjerkan et al., 2021)
Host Response

Mouse Response

  • Host Strain: Female BALB/c mice
  • Vaccination Protocol: For intramuscular (i.m.) delivery of DNA vaccines, mice were shaved on each leg, and 25 µg of PfRH5ΔNL-containing DNA or 2.5 µg of PvDBP-containing DNA was injected in a 50 µl volume into each quadriceps femoris muscle (50 µg or 5 µg total DNA/mouse, respectively). Immediately after injection, electrical pulses were applied at the injection site. BALB/c mice were immunized three times at three weeks intervals, with 50 µg plasmids that encoded either MHCII-targeted or non-targeted Vaccibodies, or antigen alone. (Bjerkan et al., 2021)
  • Immune Response: Vaccination with the MHCII-targeted vaccine showed significantly increased levels of total PfRH5FL-specific IgG compared to vaccination with the antigen alone at days 41 and 62 post-prime vaccination. The results showed that vaccination with the MHCII-targeted-PfRH5ΔNL vaccine induced significantly higher levels of IFN-γ producing cells in response to PfRH5FL protein in both spleens and dLNs as compared to vaccination with the non-targeted control vaccine and PfRH5ΔNL antigen alone. Strong and comparable levels of GIA were detected for IgG raised following DNA vaccination with PfRH5ΔNL-containing vaccines and the PfRH5ΔNL control vaccine. (Bjerkan et al., 2021)
References
Bjerkan et al., 2021: Bjerkan L, Visweswaran GRR, Gudjonsson A, Labbé GM, Quinkert D, Pattinson DJ, Spång HCL, Draper SJ, Bogen B, Braathen R. APC-Targeted DNA Vaccination Against Reticulocyte-Binding Protein Homolog 5 Induces Plasmodium falciparum-Specific Neutralizing Antibodies and T Cell Responses. Frontiers in immunology. 2021; 12; 720550. [PubMed: 34733274].