A Review on Chikungunya Virus Epidemiology, Pathogenesis and Current Vaccine Development

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in many parts of the world causing large-scale outbreaks. CHIKV infection presents as a febrile illness known as chikungunya fever (CHIKF). Infection is self-limited and characterized mainly by severe joint pain and myalgia that can last for weeks or months; however, severe disease presentation can also occur in a minor proportion of infections. Among the atypical CHIKV manifestations that have been described, severe arthralgia and neurological complications, such as encephalitis, meningitis, and Guillain–Barré Syndrome, are now reported in many outbreaks. Moreover, death cases were also reported, placing CHIKV as a relevant public health disease. Virus evolution, globalization, and climate change may have contributed to CHIKV spread. In addition to this, the lack of preventive vaccines and approved antiviral treatments is turning CHIKV into a major global health threat. In this review, we discuss the current knowledge about CHIKV pathogenesis, with a focus on atypical disease manifestations, such as persistent arthralgia and neurologic disease presentation. We also bring an up-to-date review of the current CHIKV vaccine development. Altogether, these topics highlight some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development and clinical trials of CHIKV potential vaccine candidates.

Effectiveness of CHIKV vaccine VLA1553 demonstrated by passive transfer of human sera

“…Specifically, South America and Southeast Asia were affected by outbreaks in recent years (6,7). CHIKV infections are characterized by acute febrile disease accompanied by headache, muscle pain, and skin rash, which results in chronic and incapacitating arthralgia in up to 60% of patients (8)(9)(10). Furthermore, patients may suffer from severe and often debilitating joint pain, which can persist for years, especially in adults (11,12).…”

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

“…Chikungunya virus (CHIKV) is a re-emerging arbovirus that causes a disease known as chikungunya fever (CF). This disease is characterized by intense acute inflammation, and it is accompanied by several symptoms, including fever, skin rash, muscle pain, and severe joint pain (polyarthralgia) [ 1 , 2 ]. Acute CHIKV infection induces robust innate and adaptive immune responses characterized by a high systemic production of inflammatory mediators, including IL-6 and IL-1β [ 3 , 4 ].…”

“…Acute CHIKV infection induces robust innate and adaptive immune responses characterized by a high systemic production of inflammatory mediators, including IL-6 and IL-1β [ 3 , 4 ]. Furthermore, CD4 and CD8 T cells are mainly involved in joint damage seen in CHIKV disease [ 2 ]. At the same time, innate immune cells such as neutrophils and monocytes are recruited to the infection site [ 5 , 6 ].…”

“…These disorders are known as chronic chikungunya arthritis and may last for several months or years [ 11 ]. Sometimes the pain associated with this illness can be so intense that it disrupts lifestyle, work and personal life, hampering the ability to perform simple activities [ 2 , 12 ]. Curiously, chronic diseases are characterized by impairment of natural resolution mechanisms, as already demonstrated in the literature [ 13 , 14 , 15 , 16 ].…”

“…Nevertheless, treatment remains primarily supportive since no antiviral drug is available. Management includes administration of non-steroidal anti-inflammatory drugs, other analgesic medication, rehydration, and rest [ 2 , 13 ]. We have argued that understanding mechanisms involved in controlling acute inflammation may lead to the development of new therapeutic strategies to treat viral infections, including that caused by CHIKV [ 18 , 19 ].…”