Evaluation of recombinant E2 protein-based and whole-virus inactivated candidate vaccines against Chikungunya virus
Autor(es): Kumar Manish, Sudeep A B, Arankalle Vidya A
Resumo: With the re-emergence of chikungunya virus (CHIKV) in an explosive form - in the absence of a commercially available vaccine, we aimed to develop c-idate vaccines employing recombinant E2 protein or chemically inactivated whole virus. E2 gene of CHIKV isolate of ECSA genotype was cloned in pET15b vector, expressed - purified (rE2p). The virus was propagated in Vero cell line, purified - inactivated with formalin - BPL individually. Six to eight weeks old female BALB/c mice were immunized intramuscularly with two doses of 10?g, 20?g - 50?g of vaccine formulations with or without adjuvants, 2 weeks apart. The adjuvants evaluated were alum, Mw, CadB (rE2p), alum/Mw (formalin inactivated CHIKV) - alum (BPL-inactivated CHIKV). Humoral immunity was assessed by ELISA - in vitro neutralization test using homologous - heterologous (Asian genotype) strains of CHIKV. Two cohorts of vaccinated mice were challenged separately via intranasal route with homologous virus two - 20 weeks after the 2nd dose. Viral load (CHIKV RNA by real time PCR) was determined in the serum - tissues (muscle, brain, spleen) of the mice challenged with the homologous virus. Anti-CHIK-antibody titres were dose dependent for all the immunogen formulations. BPL-inactivated vaccines led to the highest ELISA/neutralizing antibody (nAb) titres while alum was the most effective adjuvant. Asian genotype strain could be neutralized by the nAbs. In an adult mouse model, complete protection was offered by the alum-adjuvanted rE2p - both the inactivated vaccines as no virus was detected in the tissues - blood after challenge 2 weeks or 20 weeks-post-2nd dose. However, with rE2p-CadB, very low viremia was recorded on the 2nd day-post-challenge. Both rE2p - BPL/formalin-inactivated virus are promising c-idate vaccines deserving further evaluation.
Palavras-Chave: Chikungunya recombinant E2 protein; Inactivated vaccines; Viral load; Sterilizing immunity
Imprenta: Vaccine, v. 30, n. 43, p. 6142-6149, 2012
Identificador do objeto digital: 10.1016/j.vaccine.2012.07.072
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Antibodies ; Chikungunya virus - Cytokines ; Chikungunya virus - Serology ; Chikungunya virus - Viral infections ; Chikungunya virus - Real Time PCR ; Chikungunya virus - Serology ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology
Data de publicação: 2012
