Intrarectal immunization of mice with VP6 and either LT(R192G) or CTA1-DD as adjuvant protects against fecal rotavirus shedding after EDIM challenge.
Intranasal or oral delivery of the chimeric rotavirus VP6 protein MBP::VP6 to mice elicited >90% reductions in fecal rotavirus shedding after murine rotavirus challenge. Protection depended on co-administration of adjuvants, the most effective being bacterial toxins. Because of safety and efficacy concerns following intranasal or oral toxin delivery, protective efficacy of MBP::VP6 after intrarectal delivery with toxin adjuvants was determined and compared to that induced after intranasal and oral immunization. Adult BALB/c mice were orally challenged with the murine rotavirus strain EDIM 4 weeks after their second immunization with MBP::VP6 and either LT(R192G), an attenuated Escherichia coli heat-labile toxin, or CTA1-DD, a cholera toxin derivative. Reductions in fecal rotavirus shedding were then determined relative to mock-immunized mice. Immunization with MBP::VP6 and either adjuvant by any route (except oral immunization with CTA1-DD) significantly (P<0.0001) reduced rotavirus shedding. As was previously found after oral and intranasal immunization, intrarectal immunization with MBP::VP6 and adjuvant was associated with T cell responses (IFNgamma and IL-17) but not B cell (antibody) responses.
McNeal
Monica M
MM
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Basu
Mitali
M
Bean
Judy A
JA
Clements
John D
JD
Lycke
Nils Y
NY
Ramne
Anna
A
Löwenadler
Björn
B
Choi
Anthony H-C
AH
Ward
Richard L
RL
D000276:Adjuvants, Immunologic; D000285:Administration, Rectal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D036022:Capsid Proteins / Q000008:administration & dosage / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D005243:Feces / Q000821:virology*; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D015854:Up-Regulation; D017201:Virus Shedding / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D001427:Bacterial Toxins; D051792:Basic Helix-Loop-Helix Proteins; D036022:Capsid Proteins; D002772:Cholera Toxin; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D020381:Interleukin-17; D011993:Recombinant Fusion Proteins; C440610:CTA1-DD protein, recombinant; C095572:Hand1 protein, mouse; C061332:VP6 protein, Rotavirus; C027538:heat-labile enterotoxin, E coli