Mucosal and systemic antibody responses and protection induced by a prime/boost rotavirus-DNA vaccine in a gnotobiotic pig model

• Published in: Vaccine 2005-06, Vol.23 (30), p.3925-3936
• Main Authors: Yuan, Lijuan, Azevedo, Marli S.P., Gonzalez, Ana M., Jeong, Kwang-il, Van Nguyen, Trang, Lewis, Peggy, Iosef, Cristiana, Herrmann, John E., Saif, Linda J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antibodies, Viral - analysis; Antibodies, Viral - biosynthesis; Applied microbiology; Biological and medical sciences; Deoxyribonucleic acid; Diarrhea; Diarrhea - prevention & control; Diarrhea - virology; DNA; DNA vaccine; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Germ-Free Life; Gnotobiotic pigs; Hogs; Human rotavirus; Humans; Immunity, Mucosal - immunology; Immunization Schedule; Immunization, Secondary; Immunoglobulin A - analysis; Immunoglobulin A - immunology; Immunoglobulin G - analysis; Immunoglobulin G - immunology; Intestines - immunology; Kinetics; Lymphatic System - immunology; Microbiology; Miscellaneous; Plasmids; Plasmids - genetics; Rodents; Rotavirus; Rotavirus - immunology; Rotavirus Infections - immunology; Rotavirus Infections - prevention & control; Rotavirus Vaccines - genetics; Rotavirus Vaccines - immunology; Swine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - genetics; Vaccines, DNA - immunology; Viral Plaque Assay; Virology; Virus Shedding
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.03.009

A live rotavirus prime/DNA boost vaccine regimen was evaluated in a gnotobiotic pig model for human rotavirus (HRV) diarrhea. Plasmid DNA expressing rotavirus inner capsid VP6 was administered to pigs intramuscularly (IM) twice after oral priming with attenuated (Att) Wa strain HRV (AttHRV/VP6DNA2x). Other groups included: (1) VP6 DNA IM 2x then AttHRV orally (VP6DNA2x/AttHRV); (2) VP6 DNA IM 3x (VP6DNA3x) and controls. Significant protection (70%) against virus shedding, but lower protection against diarrhea (30%) was achieved only in the AttHRV/VP6DNA2x group after challenge (virulent Wa HRV). The other vaccines (VP6DNA2x/AttHRV and VP6DNA3x) were less effective. Higher protection rates were associated with the highest IgA antibody responses induced by the AttHRV/VP6DNA2x regimen. Interestingly, the VP6 DNA vaccine, although not effective when administered alone, boosted neutralizing and VP4 antibody titers in pigs previously primed with AttHRV, possibly mediated by cross-reactive T helper cells.