Protection against rotavirus shedding after intranasal immunization of mice with a chimeric VP6 protein does not require intestinal IgA.
Intranasal immunization of mice with chimeric VP6 and the adjuvant LT(R192G) consistently elicits >95% reductions in fecal rotavirus shedding following challenge. To determine the association between mucosal antibody and protection, we immunized BALB/c wt and J chain knockout (Jch-/-) mice with VP6 and either LT(R192G) or cholera toxin (CT). Both strains developed nearly equal levels of serum rotavirus IgG, but Jch-/- mice, which cannot transport dimeric IgA across epithelial cell surfaces, developed >4-fold higher levels of serum rotavirus IgA. Stool rotavirus IgA was present in wt but undetectable in Jch-/- mice. When challenged with rotavirus strain EDIM, reductions in rotavirus shedding were nearly identical in VP6-immunized wt and Jch-/- mice (i.e., 97% and 92%, respectively; P > 0.01). Th1 CD4 T cell responses were also detected in VP6-immunized animals based on high levels of IFN-gamma and IL-2 found after in vitro VP6 stimulation of spleen cells. Therefore, protection induced by intranasal immunization of mice with VP6 and adjuvant does not depend on intestinal rotavirus IgA antibody but appears to be associated with CD4 T cells.
McNeal
Monica M
MM
Division of Infectious Diseases, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
Stone
Susan C
SC
Basu
Mitali
M
Bean
Judy A
JA
Clements
John D
JD
Hendrickson
Barbara A
BA
Choi
Anthony H-C
AH
Ward
Richard L
RL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000276:immunology; D005434:Flow Cytometry; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012401:Rotavirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D012400:Rotavirus Infections / Q000276:immunology* / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D017201:Virus Shedding
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D001427:Bacterial Toxins; D036022:Capsid Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007376:Interleukin-2; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli