Chikungunya, a viral disease transmitted primarily by Aedes mosquitoes, has become a significant public health concern due to its debilitating symptoms and rapid global spread. Characterized by severe joint pain, fever, and rash, Chikungunya poses a considerable challenge for vaccine and therapeutic development. Our company provides comprehensive solutions including preclinical research, vaccine formulation and therapeutic development.
Overview of Chikungunya
Chikungunya virus (CHIKV) is an arthritogenic virus belonging to the Alphavirus genus within the Togaviridae family. The virus was first identified in the early 1950s during an outbreak in Tanzania and has since emerged as a significant public health threat globally. CHIKV is primarily transmitted to humans through the bites of infected Aedes mosquitoes, particularly Aedes aegypti and Aedes albopictus. Infection typically results in a debilitating febrile illness characterized by high fever, rash, and severe joint pain, which can persist for months or even years, leading to chronic arthralgia in some cases.
Fig.1 Schematic representation of the CHIKV genome. (Schmidt C., et al., 2022)
Vaccine Development for Chikungunya
- Virus-Like Particles (VLPs)
Virus-like particles are non-infectious structures that mimic the virus's native architecture, containing viral proteins but lacking viral genetic material. VLPs have gained traction in vaccine development due to their ability to elicit strong humoral and cellular immune responses. Studies have shown that VLPs derived from CHIKV can effectively induce neutralizing antibodies and provide protection in animal models, highlighting their potential as a safe and effective vaccine platform.
- Chimeric Vaccines
Chimeric vaccines combine genetic material from CHIKV with other viral vectors to enhance immunogenicity. Several approaches have been pursued, including:
Measles Virus-Based Chimeras
These utilize the measles virus backbone to express CHIKV proteins, leveraging the strong immunogenicity of measles vaccines. Early clinical trials indicate promising safety and immunogenicity profiles.
Alphavirus-Based Chimeras
Constructed using related alphaviruses, these vaccines can stimulate robust immune responses. Research has demonstrated their potential in animal models, suggesting a viable path toward human trials.
Vaccinia Virus-Based Chimeras
This method employs the vaccinia virus to deliver CHIKV antigens. Preliminary studies show strong immune responses in vaccinated individuals, warranting further investigation.
Therapeutics Development for Chikungunya
Therapy development for Chikungunya has seen significant advancements in recent years, focusing on antiviral compounds, immunomodulatory therapies, and host-targeting approaches. Antiviral therapies aim to inhibit viral replication, while immunomodulatory therapies seek to regulate the host immune response to alleviate symptoms and prevent long-term complications. Host-targeting therapies, on the other hand, focus on inhibiting host factors essential for viral replication.
Table 1 Therapeutic candidates under development and primary characteristics of each candidate. (Schmidt C., et al., 2022)
|
Type of therapeutic |
Compound(s) |
Model system(s) |
CHIKV strain(s) (genotype) |
| Known antiviral |
Ribavirin |
Vero cell culture |
Ross C347 (ECSA) |
| Ribavirin and interferon alpha |
Vero cell culture |
181/25 (vaccine strain) (Asian) |
| Ribavirin and doxycycline |
Vero cell culture, ICR mice |
Clinical isolate (ECSA) |
| Picolinic acid |
Vero cell culture |
DRDE-06 (ECSA) |
| Niclosamide |
BHK-21 cell culture |
S27 (ECSA), 0611aTw (ECSA), 0810bTw (ECSA) |
| Nitazoxanide |
BHK-21 cell culture |
S27 (ECSA), 0611aTw (ECSA), 0810bTw (ECSA) |
| Curcumin |
HeLa, BHK-21, Vero E6 |
06-049 (ECSA |
| Known antimicrobial |
Flavaglines |
HEK293T17 cell culture |
Thai isolate (ECSA) |
| Suramin |
BHK-21, U2O8, MRC-5 cell culture |
S27 (ECSA) |
| Flavanoid (silymarin) |
Vero, BHK-21 cell culture |
My/065/08/FN295485 (ECSA) |
| Flavonoid (baicalein) |
Vero cell culture |
FN295485 (ECSA) |
| Cardiac glycoside (lanatoside C) |
BHK cell culture |
D1225Y08 (ECSA) |
| Cardiac glycoside (lanatoside C) |
BHK cell culture |
D1225Y08 (ECSA) |
| Designer molecules |
nsP2 protease inhibitors (dimethyl benzaldehyde derivative) |
BHK-21 cell culture |
LR2006 OPY1 (ECSA) |
| Benzimidazole derivative (compound A) |
Vero cell culture |
SL10571, S27, (ECSA) BaH306 (Asian) |
| Nucleic acids |
Oligonucleotide (PMO) targeting AUG of ORFs |
HeLa cell culture |
SGEHICHD122508 (ECSA) |
| siRNA (against nsP3, E1) |
Vero E6 cell culture |
DRCE06 (ECSA) |
| siRNA (against nsP1, E2) |
Vero E6 cell culture |
061573 (ECSA) |
| Monoclonal antibodies |
Human MAb C9 |
HEK293T cell culture |
S27 (ECSA) |
| Mouse MAb CK47 (anti-E1) |
293, Vero, B7, PAI cell culture |
SL11131, clinical isolate (ECSA) |
| Host cell targets |
Prostratin |
BGM, Vero, HEL, CRL-2522 cell culture |
CHIKV-899 (ECSA) |
| Multiple small-molecule inhibitors (i.e., TOFA, pimozide) |
HEK293 cell culture |
C21 (not specified) |
Our Services
With our robust expertise and extensive capabilities, our company offers a full suite of services focused on advancing vaccines and therapies for Chikungunya. Utilizing state-of-the-art technologies and methodologies, we expedite the identification and development of promising solutions in this field.
Disease Models
- Lethal Neonatal Challenge Models
- Immunocompromised Models of Lethal Disease
- Arthritis/Myositis Models
- Chronic/Persistent Models
- Nonhuman Primate (NHP) Models
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
- Customized Research Services
Our preclinical research services provide the foundational scientific support necessary for the development of vaccines and therapies. We offer a range of services, including viral characterization, immunological assessments, and efficacy testing in animal models, ensuring that our clients have the data and insights needed to advance their products through the development pipeline. If you are interested in our services, please feel free to contact us.
References
- Schmidt, Christin, and Barbara S. Schnierle. "Chikungunya vaccine candidates: current landscape and future prospects." Drug Design, Development and Therapy (2022): 3663-3673.
- Powers, Ann M. "Vaccine and therapeutic options to control chikungunya virus." Clinical microbiology reviews 31.1 (2018): 10-1128.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
