title: 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.
abstract: 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 microg doses of EDIM VP6 and 10 microg 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 microg 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.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Choi
authors.forename: Monica M
authors.initials: MM
authors.lastname: McNeal
authors.forename: Mitali
authors.initials: M
authors.lastname: Basu
authors.forename: Jason A
authors.initials: JA
authors.lastname: Flint
authors.forename: Susan C
authors.initials: SC
authors.lastname: Stone
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Judy A
authors.initials: JA
authors.lastname: Bean
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Poe
authors.forename: John L
authors.initials: JL
authors.lastname: VanCott
authors.forename: Richard L
authors.initials: RL
authors.lastname: Ward
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000956:Antigens, Viral; D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006183:H-2 Antigens; D006801:Humans; D007114:Immunization; D051379:Mice; D008815:Mice, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012401:Rotavirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000235:genetics; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; D006183:H-2 Antigens; D011993:Recombinant Fusion Proteins; D022243:Rotavirus Vaccines; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic