Upcoming Vaccines
Chikungunya
In this chapter:
Introduction
Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), a Togaviridae virus. During epidemics and endemic circulation, CHIKV is transmitted by Aedes aegypti and, to a lesser extent, by A. albopictus mosquitoes. In Asia, CHIKV is endemic and causes recurrent and sometimes large epidemics, especially in the Indian subcontinent and in Southeast Asia. The number of reported Chikungunya cases in Malaysia is shown in Table 20.1.
Table 20.1 The number of reported Chikungunya cases in Malaysia (MOH 2020)
Chikungunya virus causes clinical illness in 72% to 92% of infected humans around four to seven days after an infected mosquito bite. Infection with CHIKV typically causes a self-limiting febrile illness, acute onset of fever, characterised by chronic, severe joint and muscle pain, and sometimes accompanied by an itchy maculopapular skin rash. Severe complications, such as encephalitis, may occur in the elderly and in individuals with comorbidities. Peripartum infections can be fatal or involve severe neurologic sequelae in foetuses and infants. Persistent arthralgia and joint swelling are common long-term manifestations of CHIKV infection. Fatalities have been reported (case fatality rates of 0.1% to 4.9% from epidemics) in elderly patients, who are at a higher risk.
There is no specific treatment available, and no licensed vaccines to specifically target CHIKV disease. Prevention of transmission is based on vector control, which is challenging especially in developing countries. Due to the epidemic potential, the impact of CHIKV infection in terms of burden of disease, work and school absenteeism, and other financial costs is particularly high.
Vaccines
There is no commercial vaccine against CHIKV at present. Several inactivated and attenuated vaccine candidates and a variety of strategies have been tested in preclinical and human trials, with promising results. The CHIKV antigen variety is limited and infection may lead to lifelong immunity. The potential vaccine candidates are classified into seven types: inactivated vaccine, subunit vaccine, live attenuated vaccine, recombinant virusvectored vaccine, virus-like particle vaccine, chimeric vaccine, and nucleic acid vaccine. About 30 vaccine candidates have been reported, but only a few have entered Phase 1 or 2 trials.
- TSI-GSD-218 (181/clone25)
Developed by United States Army Medical Research Institute of Infectious Diseases. It is a live-attenuated CHIKV strain, which completed Phase 2 trial. - VRC-CHKVLP059-00-VP (PXVX0317 CHIKV-VLP)
Developed by US National Institutes of Health. Virus-like particles (VLPs), assembled from CHIKV proteins expressed in mammalian cells. Currently in Phase 2 trial. - MV-CHIK
Developed by Institut Pasteur, Themis Bioscience. Viral vector vaccine, which is a recombinant live-attenuated measles vaccine as a vector, expressing CHIKV virus-like particles derived from the structural protein genes. Currently in Phase 2 trial.
Although VLP- and MV-based vaccines have high safety profiles, the cost of production and the potential requirement for additional boosters may hinder widespread use in low-resource countries where CHIKV is endemic.
References
Chang, L. J., Dowd, K. A., Mendoza, F. H., Saunders, J. G., Sitar, S., Plummer, S. H., Yamshchikov, G., Sarwar, U. N., Hu, Z., Enama, M. E., Bailer, R. T., Koup, R. A., Schwartz, R. M., Akahata, W., Nabel, G. J., Mascola, J. R., Pierson, T. C., Graham, B. S., Ledgerwood, J. E., & VRC 311 Study Team (2014). Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. Lancet (London, England), 384(9959), 2046–2052. https://doi.org/10.1016/S0140- 6736(14)61185-5
- Erasmus, J. H., Rossi, S. L., & Weaver, S. C. (2016). Development of Vaccines for Chikungunya Fever. The Journal of infectious diseases, 214(suppl 5), S488–S496. https://doi.org/10.1093/infdis/jiw271
- Gao, S., Song, S., & Zhang, L. (2019). Recent Progress in Vaccine Development Against Chikungunya Virus. Frontiers in microbiology, 10, 2881. https://doi.org/10.3389/fmicb.2019.02881
- Powers A. M. (2017). Vaccine and Therapeutic Options To Control Chikungunya Virus. Clinical microbiology reviews, 31(1), e00104-16. https://doi.org/10.1128/CMR.00104-16
- Ramsauer, K., Schwameis, M., Firbas, C., Müllner, M., Putnak, R. J., Thomas, S. J., Despr.s, P., Tauber, E., Jilma, B., & Tangy, F. (2015). Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial. The Lancet. Infectious diseases, 15(5), 519–527. https://doi.org/10.1016/S1473-3099(15)70043-5
- Rezza, G., & Weaver, S. C. (2019). Chikungunya as a paradigm for emerging viral diseases: Evaluating disease impact and hurdles to vaccine development. PLoS neglected tropical diseases, 13(1), e0006919. https://doi.org/10.1371/journal. pntd.0006919
- Smalley, C., Erasmus, J. H., Chesson, C. B., & Beasley, D. (2016). Status of research and development of vaccines for chikungunya. Vaccine, 34(26), 2976–2981. https://doi.org/10.1016/j.vaccine.2016.03.076
- Weaver, S. C., & Lecuit, M. (2015). Chikungunya virus and the global spread of a mosquito-borne disease. The New England journal of medicine, 372(13), 1231–1239. https://doi.org/10.1056/NEJMra1406035
- Yang, S., Fink, D., Hulse, A., & Pratt, R. D. (2017). Regulatory considerations in development of vaccines to prevent disease caused by Chikungunya virus. Vaccine, 35(37), 4851–4858. https://doi.org/10.1016/j.vaccine.2017.07.0