Nature and duration of protective immunity to bluetongue virus infection

Genetic engineering offers a variety of approaches to producing viral vaccines. An exciting advance in this field is the ability to construct virus-like particles (VLPs) that resemble their natural counterparts but lack genetic information. To develop a rationally designed vaccine for bluetongue disease of sheep that is caused by virus (BTV), we have synthesised individual BTV proteins and BTV-like particles (VLPs and CLPs) using baculovirus expression systems and insect cell cultures. A series of clinical trials were undertaken using these proteins and particles in BTV-susceptible sheep. The accumulated data obtained from these studies are: (i) the two surface proteins when used in high doses (approximately 100 microg/dose) could afford complete protection in sheep against virulent virus challenge; (ii) in contrast, only 5-10 microg of VP2 of a related virus, African horse sickness virus (AHSV) afforded protection in horses against virulent virus challenges when vaccinated in the presence of appropriate adjuvant; (iii) vaccination with as little as 10 microg VLPs (consisting of all four major proteins) gave long lasting protection (at least for 14 months) against homologous BTV challenge; (iv) cross-protection was also achieved depending on the challenge virus and amounts of antigen used for vaccination and (v) limited vaccination trials with CLPs (containing only two highly conserved internal proteins) afforded partial (with slight fever) protection against homologous and heterologous virus challenges. Since CLPs are conserved across the twenty four BTV serotypes, CLPs could have potential for a candidate vaccine that may at least mitigate the disease and inhibit virus spread. In summary, VLPs and CLPs offer completely safe and efficacious vaccines as their particles are devoid of any detectable amount of insect, baculovirus proteins or nucleic acids and thus pose no potential adverse effects.