Fighting back against chikungunya
Authors: Penny A Rudd, Suresh Mahalingam
Journal: The Lancet Infectious Diseases (2015)

Chikungunya is a mosquito-borne disease that leaves the afflicted patient with incapacitating arthritis that can last for several months or even years.1Burt FJ Rolph MS Rulli NE Mahalingam S Heise MT Chikungunya: a re-emerging virus.Lancet. 2012; 379: 662-671Summary Full Text Full Text PDF PubMed Scopus (478) Google Scholar Since the start of the largest ever outbreak of chikungunya virus infecton in 2005 in the Indian Ocean, there has been a resurgence in chikungunya cases that continues to this day.1Burt FJ Rolph MS Rulli NE Mahalingam S Heise MT Chikungunya: a re-emerging virus.Lancet. 2012; 379: 662-671Summary Full Text Full Text PDF PubMed Scopus (478) Google Scholar Adaptation of chikungunya virus to the globally distributed Asian tiger mosquito (Aedes albopictus) has led to autochthonous cases in both Europe and the Americas.2Tsetsarkin KA Vanlandingham DL McGee CE Higgs S A single mutation in chikungunya virus affects vector specificity and epidemic potential.PLoS Pathog. 2007; 3: e201Crossref PubMed Scopus (1147) Google Scholar In the year after chikungunya virus first appeared in the Caribbean, an estimated 1 million cases were reported, with concerns that the virus could spread extensively throughout the Americas.3Johansson MA Chikungunya on the move.Trends Parasitol. 2015; 31: 43-45Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar Despite the emerging importance of chikungunya virus, no specific treatment or vaccine is available for infected individuals. In The Lancet Infectious Diseases, Katrin Ramsauer and colleagues4Ramsauer K Schwameis M Firbas C et al.Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active comparator, first-in-man trial.Lancet Infect Dis. 2015; (published online March 2.)http://dx.doi.org/10.1016/S1473-3099(15)70043-5PubMed Google Scholar report promising results from a randomised, phase 1, active-comparator trial assessing the immunogenicity, safety, and tolerability of a live recombinant measles-virus-based chikungunya vaccine. Ideal vaccine candidates need to be safe, induce humoral and cellular immunity, and should provide long-lasting protection with one or just a few doses. Ramsauer and colleagues' use of the attenuated measles virus Schwarz strain is a good technique. The measles virus vaccine is one of the safest on the market and has been mass-produced at low cost in many countries since the early 1960s. The vaccine has stood the test of time and meets all the above criteria by being extremely safe and effective.5Hilleman MR Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications.Vaccine. 2001; 20: 651-665Crossref PubMed Scopus (85) Google Scholar Furthermore, measles virus is an ideal vaccine vector because it is easy to manipulate via reverse genetics, insertion of foreign sequences is well tolerated, and the resulting recombinant viruses are highly stable. 6Billeter MA Naim HY Udem SA Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.Curr Top Microbiol Immunol. 2009; 329: 129-162PubMed Google Scholar Being an RNA virus, replication is limited to the cytoplasm of cells, thereby increasing its safety. These properties make measles virus an obvious choice as a vaccine vector for various illnesses, such as those caused by Nipah virus, West Nile virus, respiratory syncytial virus, HIV, dengue virus, and severe acute respiratory syndrome coronaviruses. 5Hilleman MR Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications.Vaccine. 2001; 20: 651-665Crossref PubMed Scopus (85) Google Scholar, 6Billeter MA Naim HY Udem SA Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.Curr Top Microbiol Immunol. 2009; 329: 129-162PubMed Google Scholar, 7Escriou N Callendret B Lorin V et al.Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein.Virology. 2014; 452–53: 32-41Crossref Scopus (55) Google Scholar, 8Yoneda M Georges-Courbot MC Ikeda F et al.Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.PLoS One. 2013; 8: e58414Crossref PubMed Scopus (77) Google Scholar, 9Stebbings R Fevrier M Li B et al.Immunogenicity of a recombinant measles-HIV-1 clade B candidate vaccine.PLoS One. 2012; 7: e50397Crossref PubMed Scopus (34) Google Scholar In Ramsauer and colleagues' clinical trial, 42 healthy adults (aged 18–45 years) were assigned to receive three different doses (low, medium, or high) of the recombinant measles-virus-based chikungunya candidate vaccine, with a booster immunisation at either 28 or 90 days after the initial vaccination. All doses of the candidate vaccine were effective, albeit with varying rates of seroconversion after the primary immunisation (44% in the low-dose group, 92% in the medium-dose group, and 90% in the high-dose group). However, 100% of participants had seroconverted after the second vaccination. Pre-existing antibodies against measles did not interfere with immunogenicity of the candidate vaccine10Brandler S Ruffie C Combredet C et al.A recombinant measles vaccine expressing chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with chikungunya virus.Vaccine. 2013; 31: 3718-3725Crossref PubMed Scopus (131) Google Scholar—an important feature of this vaccine candidate in view of the high compliance rate for measles virus vaccination (around 84% worldwide). The safety profile of the candidate vaccine was deemed acceptable, with seven severe adverse events recorded in six patients (17% of participants receiving vaccinations). This proportion accords with the 5–15% of patients who develop systemic reactions after a monovalent measles vaccination. The adverse events reported included nasopharyngitis, oropharyngeal pain, headache, injection-site pain, influenza-like illness, and musculoskeletal pain. Despite the generally acceptable tolerability profile, one in six patients is a fairly concerning figure and this aspect will need to be carefully followed up in future trials. So far, this candidate vaccine is only the third chikungunya vaccine to be studied in a phase 1 setting. Strategies used for the other two vaccines differed slightly from those used in the present study. Investigators of the first study used a live-attenuated virus as a means of vaccination, whereas the investigators of the other study chose to produce a virus-like particle vaccine (VRC-CHKVLP059-00-VP).11Edelman R Tacket CO Wasserman SS Bodison SA Perry JG Mangiafico JA Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.Am J Trop Med Hyg. 2000; 62: 681-685PubMed Google Scholar, 12Chang LJ Dowd KA Mendoza FH et al.Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial.Lancet. 2014; 384: 2046-2052Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar The other candidates also yielded positive results by inducing long-lasting immunity while generating few adverse effects. Unfortunately, despite entering phase 2 trials, the first vaccine fell victim to a lack of funding and marketable interest,13Hoke Jr, CH Pace-Templeton J Pittman P et al.US Military contributions to the global response to pandemic chikungunya.Vaccine. 2012; 30: 6713-6720Crossref PubMed Scopus (45) Google Scholar and no follow-up information is available about the second candidate. Although the present phase 1 trial has only recently been published, preparations for a phase 2 trial are probably underway. Several other vaccine candidates and strategies that have yielded promising preclinical data, such as use of the picornavirus internal ribosome entry site or subunit, genetic, or recombinant modified vaccinia virus Ankara-based vaccines.14Roy CJ Adams AP Wang E et al.Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose.J Infect Dis. 2014; 209: 1891-1899Crossref PubMed Scopus (85) Google Scholar, 15Hallengard D Lum FM Kummerer BM et al.Prime-boost immunization strategies against chikungunya virus.J Virol. 2014; 88: 13333-13343Crossref PubMed Scopus (62) Google Scholar The road towards development of a vaccine approved by the US Food and Drug Administration is long and winding, but with two potential candidates in the pipeline, we might be on the right track in the fight against chikungunya. We declare no competing interests. Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial