title: Rectal immunization with rotavirus virus-like particles induces systemic and mucosal humoral immune responses and protects mice against rotavirus infection.
abstract: To evaluate whether the rectal route of immunization may be used to provide appropriate protection against enteric pathogens such as rotaviruses (RV), we studied the antibody response and the protection induced by rectal immunization of mice with RV virus-like particles (VLP). For this purpose, 6-week-old BALBc mice were rectally immunized twice with RV 8-2/6/7-VLP derived from the bovine RV RF81 strain either alone or combined with various adjuvants including four toxins [cholera toxin (CT) and three attenuated Escherichia coli-derived heat-labile toxins (LTs), LT(R192G), LT(R72), and LT(K63)] and two Toll-like receptor-targeting adjuvants (CpG and resiquimod). Six weeks after the second immunization, mice were challenged with murine RV strain ECw. RV VLP administered alone were not immunogenic and did not protect mice against RV challenge. By contrast, RV VLP combined with any of the toxin adjuvants were immunogenic (mice developed significant titers of anti-RV immunoglobulin A [IgA] in both serum and feces and of anti-RV IgG in serum) and either efficiently induced complete protection of the mice (no detectable fecal virus shedding) or, for LT(K63), reduced the amount of fecal virus shedding after RV challenge. When combined with RV VLP, CpG and resiquimod failed to achieve protection, although CpG efficiently induced an antibody response to RV. These results support the consideration of the rectal route for the development of new immunization strategies against RV infection. Rectal delivery of a VLP-based vaccine might allow the use of adjuvants less toxic than, but as efficient as, CT.
authors.affiliation: Service des Urgences Médicales Pédiatriques, Hôpital Armand Trousseau, 26 ave. du Dr Arnold Netter, 75571 Paris cedex 12, France. nathalie.parez@trs.aphp.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parez
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fourgeux
authors.forename: Ali
authors.initials: A
authors.lastname: Mohamed
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pillot
authors.forename: Axelle
authors.initials: A
authors.lastname: Dehee
authors.forename: Annie
authors.initials: A
authors.lastname: Charpilienne
authors.forename: Didier
authors.initials: D
authors.lastname: Poncet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schwartz-Cornil
authors.forename: Antoine
authors.initials: A
authors.lastname: Garbarg-Chenon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000285:Administration, Rectal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000821:virology; D005260:Female; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D017201:Virus Shedding
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022243:Rotavirus Vaccines