Table 3.
Potential assets and drawbacks of CHIK vaccines that have reached human clinical trial testing.
| VACCINE | CHIKV STRAIN | ADVANTAGE | DISADVANTAGE | CURRENT STATUS |
|---|---|---|---|---|
| VRC-CHKVLP059-00-VP133 | West African CHIKV strain 37997 | • VLPs are effective immunogens153 eliciting high titer neutralizing antibodies139 • High safety: Contains no live or replicating virus • No infection of insect cells (favorable for use in endemic regions) • No live-virus production needed • Plant-based or insect cell-based development possible140 • Phase I:133 No serious adverse events, vaccine-induced antibodies were detected in all participants up to 6 months after vaccination |
• Multiple doses required; • Adjuvant required for dose-reduction • Expensive manufacturing of in vitro VLPs48 • Large-scale DNA transfection needed153 • Lack of strategies for cost-effective production |
Finished Phase 1 in 2014 |
| CHIKV/IRESv2115 | La Réunion LR2006 OPY1 (ECSA lineage) | • High immunogenicity and long-term protection by single immunization • More stable attenuation by IRES sequence insertion compared to single point mutations • No transmission to insects/vectors • Comparably lower manufacturing costs |
• Safety concerns regarding reversion of mutation and recovering to wild type pathogenicity • Safety concerns regarding immunosuppressed conditions |
Projected for Phase 1 |
| MV-CHIK127 | La Réunion 06-46 (ECSA lineage) |
• Live attenuated Schwarz strain elicits a robust humoral and cellular immune response • Long-term experience in safety of MV as vaccine vector; contains no replicating CHIKV; replication of RNA virus is limited to cytoplasm • MV optimal vector for reverse genetics170 • No adjuvant required: comparably low effective doses • Measles vaccine can be easily produced on a large scale in most countries and distributed at low cost171 |
• Pre-existing immunity to measles may impede or prevent immunogenicity of a recombinant MV vaccine • Safety concerns about use in immunocompromised patients • Phase 1: Adverse event rate 17% (n=6) |
Finished Phase 1 in early 2015, Projected for Phase II in late 2015 |
| TSI-GSD-218132 | Clone 25/181 (SE Asian isolated strain AF15561) |
• Highly immunogenic upon one-time immunization | • Concerns about insufficient or unstable attenuation by single-point mutation • Phase 2: 8% rate of arthralgia |
Development stopped due to lack of funding |