The preclinical testing of a formaldehyde inactivated Ross River virus vaccine designed for use in humans

Abstract Ross River virus was grown in industrial facilities in vaccine-certified Vero cells in the absence of serum, inactivated using standard formalin-inactivation protocols, treated with Benzonase to digest host cell DNA and purified on a sucrose gradient. Mice given two subcutaneous injections of 0.625 μg of this vaccine or two doses of 0.156 μg vaccine with aluminium hydroxide adjuvant failed to develop a detectable viraemia after intravenous challenge with 106 TCID50 of the prototype strain of Ross River virus (T48). Guinea pigs immunised with one or two10 μg doses of vaccine with adjuvant also failed to develop a detectable viraemia following a similar challenge. The levels of neutralising antibody (neutralisation index 1.9–3.1) in the mice protected against challenge with 106 TCID50 Ross River virus were similar to those in 16 former epidemic polyarthritis patients (1.1–3.5) who had not experienced a second clinical infection with Ross River virus in the 20 years following their initial infection.