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Vaccine Detail

ChAd63/MVA Pfs25-IMX313
Vaccine Information
  • Vaccine Name: ChAd63/MVA Pfs25-IMX313
  • Target Pathogen: Plasmodium spp.
  • Target Disease: Malaria
  • Type: Recombinant vector vaccine
  • Status: Clinical trial
  • Host Species for Licensed Use: Baboon
  • Antigen: Pfs25 is a sexual stage antigen of Plasmodium falciparum that is expressed on the surface of the zygote and ookinete forms of the parasite, where it is involved in ookinete formation (de Graaf et al., 2021)
  • Pfs25 from P. falciparum 3D7 gene engineering:
    • Type: Recombinant protein preparation
    • Description: Recombinant Pfs25 was used as the vaccine antigen.
    • Detailed Gene Information: Click Here.
  • Preparation: For the Pfs25-IMX313 constructs a 229 bp DNA fragment encoding the IMX313 domain was cloned at the C-terminus of Pfs25. The Pfs25-IMX313 insert was subcloned into the ChAd63 and MVA destination and shuttle vectors. (de Graaf et al., 2021)
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: ChAd63/MVA Pfs25-IMX313 uses Pfs25, the vaccine antigen, fused to IMX313 which functions as the adjuvant, and expressed in recombinant replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and an attenuated orthopoxvirus MVA viral vectors.
Host Response

Human Response

  • Host Strain: Healthy Adults
  • Vaccination Protocol: Adults were vaccinated with 5x1010vp of ChAd63 Pfs25-IMX313 followed by 1x108pfu of MVA Pfs25-IMX313 56 days after the first vaccination. (de Graaf et al., 2021)
  • Immune Response: Vaccination with ChAd63/MVA Pfs25-IMX313 induced antigen-specific T cell responses in all volunteers; IFN-γ T cell responses were induced and peaked at median levels of greater than 2,000 SFU/million PBMCs following the MVA boost. The kinetics and magnitude of the anti-Pfs25 serum IgG antibody response were assessed over time by ELISA against Pfs25 recombinant protein. Priming vaccination with 5 × 1010 vp ChAd63 Pfs25-IMX313 followed by MVA Pfs25-IMX313 boost induced antigen-specific IgG responses in all volunteers. Median transmission reducing activity was 7.2% (range -5.8% to 37.3%) in Group 2B and 25.3% (range 10.2% to 41.3%) in Group 2C. There was no significant inhibition of oocyst intensity, further progression of research unlikely. (de Graaf et al., 2021)
  • Side Effects: There were no serious adverse events (SAEs) or unexpected reactions during the course of the trial and no volunteers withdrew due to vaccine-related adverse events (AEs). The reactogenicity of the vaccines was similar to that seen in previous malaria vaccine trials using the same viral vectors at similar doses in healthy adultswith the higher doses of both vaccines associated with an increased number of reported AEs. (de Graaf et al., 2021)
References
de Graaf et al., 2021: de Graaf H, Payne RO, Taylor I, Miura K, Long CA, Elias SC, Zaric M, Minassian AM, Silk SE, Li L, Poulton ID, Baker M, Draper SJ, Gbesemete D, Brendish NJ, Martins F, Marini A, Mekhaiel D, Edwards NJ, Roberts R, Vekemans J, Moyle S, Faust SN, Berrie E, Lawrie AM, Hill F, Hill AVS, Biswas S. Safety and Immunogenicity of ChAd63/MVA Pfs25-IMX313 in a Phase I First-in-Human Trial. Frontiers in immunology. 2021; 12; 694759. [PubMed: 34335606].