Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses

• Published in: Vaccine Vol. 20; no. 27; pp. 3310 - 3321
• Main Authors: Choi, Anthony H, McNeal, Monica M, Basu, Mitali, Flint, Jason A, Stone, Susan C, Clements, John D, Bean, Judy A, Poe, Stacey A, VanCott, John L, Ward, Richard L
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 10.09.2002; Elsevier
• Subjects: Administration, Intranasal; Administration, Oral; Animals; Antigens, Viral; Base Sequence; Biological and medical sciences; Capsid Proteins - genetics; Capsid Proteins - immunology; DNA, Viral - genetics; Escherichia coli - genetics; Female; Fundamental and applied biological sciences. Psychology; H-2 Antigens; Human rotavirus; Humans; Immunization; Mice; Mice, Inbred Strains; Microbiology; Mouse model; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Rotavirus; Rotavirus - genetics; Rotavirus - immunology; Rotavirus - isolation & purification; Rotavirus Infections - immunology; Rotavirus Infections - prevention & control; Rotavirus Infections - virology; Rotavirus Vaccines - administration & dosage; Rotavirus Vaccines - genetics; Time Factors; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Virology; VP6 vaccines; Rotavirus; Mouse model; VP6 vaccines; Recombinant microorganism; Animal model; Immunization; Treatment efficiency; Escherichia coli; Rodentia; Oral administration; Vaccine; Intranasal administration; Reoviridae; Virus; Vertebrata; Mammalia; Mouse; Immunological adjuvant; Bacteria; Enterobacteriaceae
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(02)00315-8

Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6 protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2 d) mice along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat-labile toxin, has been found to consistently stimulate ca. 99% reductions in rotavirus shedding after subsequent EDIM challenge. This study was designed to determine the robustness of this protection, i.e. can VP6 immunization consistently protect against shedding in this model, thus, providing an indication of its potential as a vaccine. Intranasal immunization with two 8.8 μg doses of EDIM VP6 and 10 μg of LT(R192G) was found to stimulate 99% reductions in EDIM shedding in four additional strains of inbred mice belonging to three haplotypes, i.e. DBA/2 (H-2 d), C57BL/6 (H-2 b), 129 (H-2 b) and C3H (H-2 k). Protection stimulated against EDIM antigen shedding following i.n. immunization with VP6 from the human CJN strain was less ( P=0.02) than induced by EDIM VP6 (86% versus 99%), but no further loss of protection was observed when the dose of CJN VP6 was reduced 100-fold. Protection against EDIM shedding was also maintained after i.n. immunization of three strains of outbred mice (CF-1, CD-1 and Swiss Webster) with either EDIM or CJN VP6, i.e. EDIM VP6 immunization reduced EDIM shedding by 99% while CJN VP6 immunization produced reductions of 86–96%. Protection stimulated by oral immunization of BALB/c mice with two 8.8 μg doses of either VP6 chimera plus LT(R192G) was not significantly different from that induced by i.n. immunization. Finally, protection found after either oral or i.n. immunization with EDIM or CJN VP6 was no different when the mice were challenged with McN, another strain of murine rotavirus. These results support further evaluation of VP6 as a vaccine.