“High Profile Diseases” are written by individual NPRC Core Scientists who are experts in the specific subject of each article. Before publication on the website, each article is reviewed by representatives of all seven NPRCs.
Chad Roy (TNPRC)
Reports over the last year have highlighted the growing concern over Chikungunya as an emerging infectious disease that holds the potential to affect a large proportion of the world’s population. Chikungunya is a vectorborne (mosquito-borne) viral disease that has taken advantage of an ecological niche to migrate into parts of the world where less than a decade ago it was nonexistent. This viral disease has a history of causing high incidence outbreaks in hyperendemic areas with limited resources and limited vector abatement controls. Recently, the incidence of Chikungunya has dramatically increased within Caribbean and Central American countries, and is poised for an appearance within the continental United States – punctuating the fluidity in which infectious disease now travels in the modern world. In contrast to diseases such as influenza, Chikungunya remains relatively understudied, and its rapid emergence has prompted a number of scientific investigations ranging from basic pathogenesis to advanced strategies for vaccine and therapeutic design and effectiveness.
Nonhuman primate studies are critical for these ongoing research efforts to understand the biological basis of this viral disease as well as evaluation of vaccines and therapeutics. One of the reasons the nonhuman primate has played such a pivotal role in Chikungunya-related research lies in the nature of the clinical disease – Chikungunya primarily causes severe morbidity (undulating fever, polyarthritis, myalgia), but rarely causes death in humans. That aspect of the disease process, which includes unusually long sequelae, is notoriously difficult to study in natural outbreaks. Experimental rodent models provide only limited insight into the complexities of such clinical manifestations. Modeling efforts in the nonhuman primates, in contrast, have yielded a better understanding of the immunopathology and correlative physiological hallmarks associated with disease. Laboratory studies using nonhuman primates have provided a robust and reproducible model for evaluation of many of the experimental vaccines under development for prevention of Chikungunya disease. This includes establishing ‘near clinical’ immunogenicity and protective efficacy of many of the leading candidate products being developed for prevention of Chikungunya, including a VLP-based vaccine 1 and a live attenuated vaccine 2. These studies and others with similar focus are viewed as highly translatable to the clinic and may accelerate the promise of future clinical trials to be performed in areas prone to Chikungunya infection. Now that Chikungunya virus infection has been identified in the continental United States, with locally acquired cases identified in Florida calls for effective, licensed treatments have increased in urgency.
1Akahata, W., Yang Z.Y., Andersen, H., Sun, S., Holdaway, H.A., Kong, W.P., Lewis, M.G., Higgs, S., Rossmann, M.G., Rao, S., Nabel GJ. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat Med,16(3):334-8. 2010.
2Roy, C.J., Adams, A.P., Wang, E., Plante, K., Gorchakov, R., Seymour, R.L., Vinet-Oliphant, H., Weaver, S.C.: Chikungunya Vaccine Candidate is Highly Attenuated and Protects Nonhuman Primates Against Telemetrically-monitored Disease Following a Single Dose. J Infec Dis. 1;31(11):1464-70, 2014.
Haese N, Powers J, Streblow DN
Small Molecule Inhibitors Targeting Chikungunya Virus.
Curr Top Microbiol Immunol. 2020 Jan 24. doi: 10.1007/82_2020_195. 2020.
Broeckel RM, Haese N, Ando T, Dmitriev I, Kreklywich CN, Powers J, Denton M, Smith P, Morrison TE, Heise M, DeFilippis V, Messaoudi I, Curiel DT, Streblow DN
Vaccine-Induced Skewing of T Cell Responses Protects Against Chikungunya VirusDisease.
Front Immunol. 2019 Oct 31;10:2563. doi: 10.3389/fimmu.2019.02563. eCollection2019. 2019.
Broeckel R, Sarkar S, May NA, Totonchy J, Kreklywich CN, Smith P, Graves L, DeFilippis VR, Heise MT, Morrison TE, Moorman N, Streblow DN
Src Family Kinase Inhibitors Block Translation of Alphavirus Subgenomic mRNAs.
Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: AAC.02325-18. doi:10.1128/AAC.02325-18. Print 2019 Apr. 2019.
Chikungunya Virus Vaccines: Platforms, Progress, and Challenges.
Curr Top Microbiol Immunol. 2019 Jul 24. doi: 10.1007/82_2019_175. 2019.
Peterson TA, MacLean AG, Russell-Lodrigue KE, Didier PJ, Weaver SC, Roy CJ
Adverse event following live attenuated chikungunya vaccine in a cynomolgusmacaque with pre-existing chronic hydrocephalus.
J Med Primatol. 2019 Aug;48(4):257-259. doi: 10.1111/jmp.12414. Epub 2019 Apr 3. 2019.
Akahata, W., Yang Z.Y., Andersen, H., Sun, S., Holdaway, H.A., Kong, W.P., Lewis, M.G., Higgs, S., Rossmann, M.G., Rao, S., Nabel GJ.
A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection.
Nat Med,16(3):334-8. 2010.
April 25, 2017
Promising Tests of a Vaccine against Chikungunya virus
November 26, 2015
Chikungunya may cause severe brain infection
November 24, 2015
Clinical trial of chikungunya vaccine opens
August 19, 2015
June 2, 2015
Chikungunya is on the move
January 22, 2015
What You Should Know About the Chikungunya Virus
December 31, 2014
Chikungunya Virus on the Move
December 15, 2014
Beware of the bite that causes chikungunya
December 4, 2014
Chikungunya has sickened more than 10,000 in Puerto Rico
November 6, 2014
Chikungunya Still a Concern for Travelers: CDC
September 27, 2014
Death Toll Climbs, as Mosquito-Borne Virus Chikungunya Sweeps Americas
September 27, 2014
Chikungunya Disease Slowly Sneaking into U.S. as World Focuses on Ebola
September 17, 2014