• Vaccine Name: CAdVax-CHIK
• Target Pathogen: chikungunya virus
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Antigen: structural polyprotein (comprising the envelope glycoproteins E1, E2 and capsid) of CHIKV (Wang et al., 2011)
• Réunion Island isolate, structural polypeptide gene engineering:
  • Type: Recombinant vector construction
  • Description: (Wang et al., 2011)
  • Detailed Gene Information: Click Here.
• Preparation: The coding sequence for the CHIKV, Réunion Island isolate, structural polypeptide was synthesized with codons optimized for expression in human cells by GeneArt (Regensburg, Germany). This gene, encoding capsid (C), E3, E2, 6K and E1, was subcloned into the 2pRAd plasmid shuttle vector. Digestion with NruI and XbaI restriction enzymes followed by ligation was used to delete the CMV promoter and bovine growth hormone polyadenylation (BGHpA) signal from the 2pLAd plasmid shuttle vector. Using these shuttle vectors the vaccine was constructed. Correct insertion was confirmed by sequencing, PCR, and restriction enzyme digestion. Vector stocks were generated on the HEK293 packaging cell line, isolated by plaque-purification, amplified, and then purified by caesium chloride gradient before final virus titration. (Wang et al., 2011)
• Immunization Route: Intraperitoneal injection (i.p.)
• Description: A recombinant vector vaccine encoding the structural poly protein of CHIKV that provides protection in mouse model. (Wang et al., 2011)

Mouse Response

• Vaccination Protocol: Female CD-1 outbred mice (Charles River Laboratory, Raleigh, NC) or female C57BL/6 mice (ARC, Perth, Australia) 6–8 weeks old were vaccinated intraperitoneally (i.p.) once with 1 × 108 infectious units of the CAdVax–CHIK vaccine, or the indicated control CAdVax vaccine in 100 μl of PBS, or 100 μl of PBS. (Wang et al., 2011)
• Immune Response: Consistent IgG responses in all outbred CD-1 CAdVax–CHIK immunised mice were apparent at week 2 post vaccination and responses peaked at week 6, with a mean end point titre of ≈1/75,000. No significant antibody reactivity to the ELISA antigen (a lysate of CAdVax–CHIK infected cells) was observed in sera from outbred CD-1 mice vaccinated once with the control CAdVax vector. C57BL/6 CAdVax–CHIK vaccinated mice showed a mean end point titre of over 1 in 3.5 × 10^6 for anti-CHIKV IgG2c. The mean IgG1 titre after CAdVax–CHIK vaccination was over 1 in 3 × 106, significantly higher than that seen after CHIKV infection. C57BL/6 mice vaccinated with the control CAdVax vector or PBS generated no detectable CHIKV-specific IgG1 or IgG2c responses. (Wang et al., 2011)
• Challenge Protocol: Six and a half weeks after vaccination mice were challenged with 1 × 10^4 CCID50 of the Réunion Island or Asian isolate s.c. into the side of each hind foot toward the ankle. The extended time between vaccination and challenge was used to avoid any influence of vector-induced interferon α/β responses, given the sensitivity of CHIKV infection to these cytokines. (Wang et al., 2011)
• Efficacy: Viraemia after challenge with the Réunion Island isolate. Viraemia was significantly different between CAdVax–CHIK and CAdVax–control vaccinated groups on days 1–3 (all p < 0.037, Mann–Whitney U-test). Foot swelling after challenge with the Réunion Island isolate. Swelling (represented as a cross sectional area in mm^2) was significantly different between CAdVax–CHIK and CAdVax–control vaccinated groups on days 3–8 (all p < 0.02, Mann–Whitney U-test). Viraemia after challenge with the Asian isolate. Viraemia was significantly different between CAdVax–CHIK and CAdVax–control vaccinated groups on days 1–4 (all p < 0.014, Mann–Whitney U-test). Foot swelling after challenge with the Asian isolate. Swelling was significantly different between CAdVax–CHIK and CAdVax–control vaccinated groups on days 3–10 (all p < 0.04, Mann–Whitney U-test). (Wang et al., 2011)