Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse model compared to glycoprotein El or E2 subunits

Chikungunya virus (CHIKV) causes acute illness characterized by fever and long-lasting arthritic symptoms. The need for a safe and effective vaccine against CHM/infections is on the rise due to on-going vector spread and increasing severity of clinical complications. Here we report the results of a comparative vaccination-challenge experiment in mice using three different vaccine candidates produced in insect cells by recombinant baculoviruses: (i) secreted (s)E1 and (ii) sE2 CHIKV glycoprotein subunits (2 mu g/immunization), and (iii) CHIKV virus-like particles (VLPs) (1 mu g E2 equivalent/immunization). These experiments show that vaccination with two subsequent administrations of 1 mu g of Matrix M adjuvanted CHIN VLPs completely protected AG129 mice from lethal CHIN challenge. Vaccination with El and E2 subunits provided partial protection, with half of the mice surviving but with significantly lower neutralizing antibody titres as compared to the VLP vaccinated mice. This study provides evidence that even a modest neutralizing antibody response is sufficient to protect mice from CHM/infections. Neutralization was the prominent correlate of protection. In addition, CHIKV VLPs provide a superior immune response and protection against CHIICV-induced disease in mice as compared to individual CHIKV-sEl and -sE2 subunits. (C) 2013 Elsevier Ltd. All rights reserved