Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles

• Published in: Vaccine Vol. 17; no. 7; pp. 1005 - 1013
• Main Authors: Jiang, Baoming, Estes, Mary K, Barone, Christopher, Barniak, Vicki, O’Neal, Christine M, Ottaiano, Adriana, Madore, H.Paul, Conner, Margaret E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 26.02.1999; Elsevier
• Subjects: Adjuvants, Immunologic - pharmacology; AIDS/HIV; Animals; Antibodies, Viral - biosynthesis; Biological and medical sciences; Feces - chemistry; Female; Fundamental and applied biological sciences. Psychology; Mice; Mice, Inbred Strains; Microbiology; Rotavirus; Rotavirus - genetics; Rotavirus - immunology; Rotavirus Infections - prevention & control; Saponins - administration & dosage; Saponins - immunology; Space life sciences; Th1 Cells - immunology; Th2 Cells - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; Viral Vaccines - immunology; Viral Vaccines - therapeutic use; Virion - immunology; Virology; Immunoprotection; Rotavirus; Digestive system; Virus like particle; Cross protection; Rodentia; Gut; Vaccine; Intramuscular administration; Reoviridae; Property formulation relationship; Virus; Vertebrata; Local immunity; Mammalia; Immunogenicity; Mouse; Immunological adjuvant; Serotype; Humoral immunity; Non-programmatic
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(98)00317-X

Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3 serotype specificity were produced in insect cells coinfected with recombinant baculoviruses expressing single rotavirus genes. The VLPs were purified and subsequently evaluated for immunogenicity and protection in the adult mouse model of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice were examined for serum and fecal antibody responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine EC wt rotavirus was assessed by comparing the antigen shed in stool of the VLP-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented antibody responses were further characterized by equivalent IgG1 and IgG2a titers in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in QS-21 induced partial protection (88%) against oral challenge with the heterotypic EC wt virus, whereas G3 VLPs in QS-21 induced complete protection (100%). In contrast, G1 VLPs when formulated with AlOH induced a predominant Th2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody responses to rotavirus VLPs and the protective efficacy against rotavirus infections. These data have important implications for the development of parenteral vaccines to ameliorate rotavirus disease.