ROTAVIRUS VIRUS-LIKE PARTICLES ADMINISTERED MUCOSALLY INDUCE PROTECTIVE IMMUNITY

We have evaluated the immunogenicity and protective efficacy of rotavi rus subunit vaccines administered by mucosal routes, Virus-like partic les (VLPs) produced by self-assembly of individual rotavirus structura l proteins coexpressed by baculovirus recombinants in insect cells wer e the subunit vaccine tested, We first compared the immunogenicities a nd protective efficacies of VLPs containing VP2 and VP6 (2/6-VLPs) and G3 2/6/7-VLPs mixed with cholera toxin and administered by oral and i ntranasal routes in the adult mouse model of rotavirus infection. VLPs administered orally induced serum antibody and intestinal immunoglobu lin A (IgA) and IgG. The highest oral dose (100 mu g) of VLPs induced protection from rotavirus challenge (greater than or equal to 50% redu ction in virus shedding) in 50% of the mice, VLPs administered intrana sally induced higher serum and intestinal antibody responses than VLPs administered orally. All mice receiving VLPs intranasally were protec ted from challenge; no virus was shed after challenge, Since there was no difference in immunogenicity or protective efficacy between 2/6- a nd 2/6/7-VLPs, protection was achieved without inclusion of the neutra lization antigens VP7 and VP4. We also tested the immunogenicities and protective efficacies of 2/6-VLPs administered intranasally without t he addition of cholera toxin. 2/6-VLPs administered intranasally witho ut cholera toxin induced lower serum and intestinal antibody titers th an 2/6-VLPs administered with cholera toxin. The highest dose (100 mu g) of 2/6-VLPs administered intranasally without cholera toxin resulte d in a mean reduction in shedding of 38%. When cholera toxin was added , higher levels of protection were achieved with 10-fold less immunoge n, VLPs administered mucosally offer a promising, safe, nonreplicating vaccine for rotavirus.