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Vaccine Detail

ChAd63-MVA AMA1
Vaccine Information
  • Vaccine Name: ChAd63-MVA AMA1
  • Target Pathogen: Plasmodium spp.
  • Target Disease: Malaria
  • Type: Recombinant vector vaccine
  • Status: Clinical trial
  • Host Species for Licensed Use: Human
  • Antigen: AMA1: apical membrane antigen 1 of P. falciparum(Sheehy et al., 2012)
  • AMA1 from P. falciparum 3D7 gene engineering:
    • Type: Recombinant protein preparation
    • Description:
    • Detailed Gene Information: Click Here.
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: Prime-boosting combination that use the same antigen but different vectors: ChAd63 MSP1 is the prime vaccination and MVA MSP1 is the booster.(Sheehy et al., 2012)
Host Response

Human Response

  • Host Strain: malaria-naive adults from Oxford area(Sheehy et al., 2012)
  • Host age: 18-48 years(Sheehy et al., 2012)
  • Host gender: 10 female, 6 male (Sheehy et al., 2012)
  • Vaccination Protocol: Phase Ia, open-label, non-randomized blood stage malaria vaccine trial
    Participants were divided into two groups: Group 1 (eight volunteers) received 5 × 10^9 viral particles ChAd63 AMA1 diluted in 0.9% NaCl and administered in 300 µL as primary vaccination, and four of these received 5 × 10^8 pfu MVA AMA1 undiluted and administered in 200 µL as booster 56 days later. Group 2 (8 volunteers) received 5 × 10^10 viral particles ChAd63 AMA1 undiluted and administered in 300 µL as primary vaccination, and four of these received MVA AMA1 as booster 56 days later: one received 2.5×10^8 pfu undiluted and administered in 100 µL, and the rest (three volunteers) received 1.25×10^8 pfu undiluted and administered in 50 µL. (Sheehy et al., 2012)
  • Immune Response: Cellular: peak of IFN-γ SFC response at day 14, no significant difference between the two groups (921 vs 933 SFU/million PBMCs in higher vs lower group). Responses contracted by day 56. After MVA MSP1: responses were significantly boosted, stronger response in the highest dose group (7186 vs 2631SFU/million PBMCs in 5×10^8 group vs lower dose group).CD4+ and CD8+ responses were detectable: CD8+ upregulated CD107a expression and produced IFN-γ and TNFα, and CD4+ produced high levels of TNFα.

    Humoral: serum IgG antibody response detectable. Peak of antibody responses against AMA1 at day 28, significantly stronger responses in the higher dose group (109 vs 37 AU). Response declined slowly but was maintained at day 90. After MVA MSP1: responses were significantly boosted and reached peak at day 84, no significant difference between the lower dose groups and the highest dose group (1709 vs 949 AU). Response declined but was maintained at day 140 (971 vs 547 AU). (Sheehy et al., 2012)
  • Side Effects: Local: swelling, pruritus, warmth, erythema, and pain. Systematic: nausea, malaise, headache, fever, feverish, fatigue, arthralgia, and myalgia
    Most AEs were mild in severity and all resolved completely. (Sheehy et al., 2012)
References
Sheehy et al., 2012: Sheehy SH, Duncan CJ, Elias SC, Biswas S, Collins KA, O'Hara GA, Halstead FD, Ewer KJ, Mahungu T, Spencer AJ, Miura K, Poulton ID, Dicks MD, Edwards NJ, Berrie E, Moyle S, Colloca S, Cortese R, Gantlett K, Long CA, Lawrie AM, Gilbert SC, Doherty T, Nicosia A, Hill AV, Draper SJ. Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors. PloS one. 2012; 7(2); e31208. [PubMed: 22363582].