Towards a Vaccine Strategy?
There is no licensed human vaccine for CHIK. The first formulation of a potential vaccine was established by the US Army and tested in the early 1970s. CHIKV was produced from monkey cell cultures and the vaccine was prepared from either formalin-fixed virus or Tween-ether-extracted viral proteins.[93,94] The inactivated CHIKV vaccine was able to stimulate antibody production with neutralizing capacities when tested on a small cohort of army recruits.
A live-attenuated strain of CHIKV was obtained from an old strain of Asian origin (Bangkok, 1962) and cultured on MRC5 (human fetal fibroblast cell line) human fibroblasts. Preclinical studies and Phase II trials were conducted on 200 healthy US Army volunteers.[96,97] Very satisfactory seroconversion rates (98% on day 28) and neutralizing antibody titers were obtained, persisting in 85% of cases at 1 year. Further development was stopped due to new priorities in the US Army and perhaps also due to the problem of potential interference arising from sequential administration of vaccines specific for different alphaviruses. For example, McClain and colleagues showed that vaccination with CHIKV followed by Venezuelan equine encephalitis virus resulted in reduced Venezuelan equine encephalitis virus-specific responses. The candidate vaccine was then stored frozen in lyophilized form. Requalification of the American candidate vaccine was decided in France, but then abandoned at the end of 2008 as the vaccine batch no longer met the demands of the French Medicine Evaluation Agency.
More recently, three new recombinant versions of CHIKV vaccines were reported and successfully tested on mouse or macaque animal models.[61,98,99] Akahata and colleagues showed that the selective expression of viral structural proteins gives rise to virus-like particles in vitro that resemble replication-competent alphaviruses. Immunization with these virus-like particles elicited neutralizing antibodies against envelope proteins. Macaques immunized with particles were protected against viremia after high-dose challenge, by producing high titers of neutralizing antibodies. Immunization with alphavirus virus-like particle vaccines may represent a new strategy to contain the spread of CHIKV-related pathogenic viruses in humans.
Expert Rev Anti Infect Ther. 2010;8(9):987-996. © 2010
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