Chikungunya Virus and Prospects for a Vaccine

Scott C Weaver; Jorge E Osorio; Jill A Livengood; Rubing Chen; Dan T Stinchcomb


Expert Rev Vaccines. 2012;11(9):1087-1101. 

In This Article

Challenges to Clinical Trials & Deployment of a Chikungunya Vaccine

Vaccination is the most cost-effective means of protecting the at-risk populations in CHIK-endemic developing countries. CHIK epidemics are explosive and rapidly moving, but not predictable. As CHIKV outbreaks occur only sporadically and unpredictably in affected countries, CHIK vaccine efficacy cannot be proven in Phase III studies, a requirement for traditional regulatory approval by the US FDA. Design of clinical trials, especially Phase II and III human trials, is difficult due to the epidemiology of CHIKV infection and disease. An option to seek licensure based on neutralizing antibody levels as a correlate of immune protection would be valuable. Data obtained so far have clearly shown that protective antibodies play a role in control of CHIKV infection. Adoptive transfer studies indicate that neutralization of viruses by anti-CHIKV antibodies protects against CHIK infection. Antibody titers are acceptable correlates of human protection for several licensed vaccines, such as the hepatitis A vaccine,[104] pneumococcal vaccine,[105,106] measles,[107] influenza[108] and others. For protecting against viruses transmitted by arthropods, such as the yellow fever vaccine, neutralizing antibodies induced by immunization correlate well with protection; a level of 0.7 neutralization units equivalent to a 1:5 titer is considered protective.[109] For Japanese encephalitis vaccines a neutralizing titer of 1:10 is thought to be protective.[110] For tick-borne encephalitis an antibody level of 125 ELISA units is protective.[111,112] Interestingly, natural CHIKV infections induce high neutralizing antibody levels varying in titer from 40 to 20,000.[41] These neutralizing antibodies have been detected in patients with CHIK early during the course of infection, and the presence of IgG antibodies correlates with viral clearance and long-term protection.[64,65] The E2 domain of the CHIKV envelope glycoprotein has been shown to bind with high affinity to CHIKV, suggesting that this epitope is responsible for virus neutralization. These data provide convincing evidence that levels of neutralizing antibodies are strongly correlated with a protective immune response. Establishing a correlate of protection would ease the regulatory path to CHIKV licensure, and accelerate the development accessibility of this important vaccine.