Extended preclinical safety, efficacy and stability testing of a live-attenuated Chikungunya vaccine candidate
Autor(es): Plante Kenneth S, Rossi Shannan L, Bergren Nicholas A, Seymour Robert L, Weaver Scott C
Resumo: We recently described a new, live-attenuated vaccine c-idate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic - efficacious in protecting against CHIK virus (CHIKV) challenge of mice - nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution - viral loads in interferon-?/? receptor-incompetent A129 mice to another CHIK vaccine c-idate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues - organs, including the brain - leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination - viral loads compared to 181/clone25, - was never found outside the blood, spleen - muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture - hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental - passaged viruses for footpad swelling, weight stability - survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from <10% to >30%) - mortality (from 0 to 100%), CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss - no mortality). These data indicate greater nonclinical safety of the CHIKV/IRES vaccine c-idate compared to 181/clone25, further supporting its eligibility for human testing.
Imprenta: PLoS Neglected Tropical Diseases, v. 9, n. 9, p. e0004007, 2015
Identificador do objeto digital: 10.1371/journal.pntd.0004007
Descritores: Chikungunya virus - Cytopathology ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever
Data de publicação: 2015
