Neonatal sublingual vaccination with Salmonella proteins and adjuvant cholera toxin or CpG oligodeoxynucleotides induces mucosal and systemic immunity in mice.
OBJECTIVE
Salmonella enteritidis is one of the most common enteric pathogens that cause acute gastroenteritis. A vaccine that can induce systemic and mucosal immune responses by a simple, noninvasive pathway and provide protection against this mucosal pathogen is needed.


METHODS
Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with sonicated Salmonella proteins (SSP) only, or SSP combined with adjuvant CpG or cholera toxin (CT). A booster vaccination was given 7 weeks after the last treatment. Serum and saliva antibody responses, cytokine profiles of spleen cells, survival rate, and intestinal morphology after live S enteritidis challenge were investigated.


RESULTS
Saliva-specific secretory IgA (SIgA) antibody responses were markedly enhanced by neonatal sublingual vaccination with SSP together with adjuvant CpG or CT. Whereas vaccination with SSP and CpG enhanced spleen cell interferon-gamma production and serum-specific IgG2a antibody responses, vaccination with SSP and CT increased spleen cell interleukin (IL)-4, IL-5, IL-6, and interferon-gamma production and serum-specific IgG1 and IgG2a antibody responses. Vaccination with SSP and CpG or CT protected against intestinal necrosis and was associated with a higher survival rate after oral challenge with live S enteritidis. The vaccinated mice with higher specific IgG and saliva-specific secretory IgA antibody levels had a better survival rate.


CONCLUSIONS
Neonatal sublingual vaccination with adjuvant CpG or CT can induce both mucosal and systemic immunity and may play a crucial role in protection against enteric pathogens.
Huang
Ching-Feng
CF
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Wang
Chih-Chien
CC
Wu
Tzee-Chung
TC
Wu
Keh-Gong
KG
Lee
Chin-Cheng
CC
Peng
Ho-Jen
HJ
D000276:Adjuvants, Immunologic; D000286:Administration, Sublingual; D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D003888:Desensitization, Immunologic; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011489:Protein Denaturation; D012463:Saliva / Q000276:immunology; D012480:Salmonella Infections / Q000453:epidemiology / Q000517:prevention & control; D022562:Salmonella Vaccines / Q000276:immunology*; D012477:Salmonella enteritidis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D022562:Salmonella Vaccines; D002772:Cholera Toxin