![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
ABSTRACT
Rotavirus (RV) and norovirus (NoV) are the 2 leading causes of acute viral gastroenteritis worldwide. We have developed a non-live NoV and RV vaccine candidate consisting of NoV virus-like particles (VLPs) and recombinant polymeric RV VP6 protein produced in baculovirus-insect cell expression system. Both components have been shown to induce strong potentially protective immune responses. As VP6 nanotubes are highly immunogenic, we investigated here a possible adjuvant effect of these structures on NoV-specific immune responses in vivo. BALB/c mice were immunized intramuscularly with a suboptimal dose (0.3 μg) of GII.4 or GI.3 VLPs either alone or in a combination with 10 μg dose of VP6 and induction of NoV-specific antibodies in sera of experimental animals were measured. Blocking assay using human saliva or synthetic histo-blood group antigens was employed to test NoV blocking antibodies. Suboptimal doses of the VLPs alone did not induce substantial anti-NoV antibodies. When co-administered with the VP6, considerable titers of not only type-specific but also cross-reactive IgG antibodies against NoV VLP genotypes not included in the vaccine composition were induced. Most importantly, NoV-specific blocking antibodies, a surrogate for neutralizing antibodies, were generated. Our results show that RV VP6 protein has an in vivo adjuvant effect on NoV-specific antibody responses and support the use of VP6 protein as a part of the NoV-RV combination vaccine, especially when addition of external adjuvants is not desirable.
Abbreviations
| RV | = | rotavirus |
| NoV | = | norovirus |
| VLPs | = | virus-like particles |
| BV | = | baculovirus |
| APC | = | antigen presenting cells |
| GI | = | genogroup I |
| GII | = | genogroup II |
| EM | = | electron microscopy |
| GMT | = | geometric mean titer |
| GII.4 NO | = | GII.4 New Orleans |
| Le | = | Lewis |
| HBGA | = | histo-blood group antigen |
| IL | = | interleukin |
| IFN-γ | = | interferon-gamma |
| CM | = | culture medium |
| BTV | = | bluetongue virus |
| TNF-α | = | tumor necrosis factor-alpha |
| SDS-PAGE | = | sodium dodecyl sulfate polyacrylamide gel electrophoresis |
| PBS | = | phosphate-buffered saline |
| ELISA | = | enzyme-linked immunosorbent assay |
| HRP | = | horseradish peroxidase |
| OPD | = | o-phenylenediamine dihydrochloride |
| OD | = | optical density |
| ELISPOT | = | enzyme-linked immunospot |
Disclosure of potential conflicts of interest
The authors report no conflicts of interest.
Acknowledgments
Technical support of K. Tamminen, H. Uusi-Kerttula, M. Karlsberg, E. Jokela, S. Kaven and N. Koivisto is greatly acknowledged. We gratefully acknowledge the technical assistance of personnel at UMN Pharma Inc., Japan.