TY - JOUR
T1 - LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1
AU - Batista, Milene Tavares
AU - Ferreira, Ewerton Lucena
AU - Pereira, Gisela de Souza
AU - Stafford, Phillip
AU - Maeda, Denicar Lina Nascimento Fabris
AU - Rodrigues, Juliana Falcão
AU - Brady, L. Jeannine
AU - Johnston, Stephen
AU - Ferreira, Luís Carlos de Souza
AU - Ferreira, Rita de Cássia Café
N1 - Funding Information:
This work was supported by the FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) – Brazil [grant 2012/51189-3 ; 2013/06671-4 ; 2015/15562-0 ] and National Institutes of Health – United States [grants DE008007 and DE021789 to LJB].
Publisher Copyright:
© 2017
PY - 2017/12/19
Y1 - 2017/12/19
N2 - In this study, we evaluated the immunogenicity, protective efficacy and peptide-based immune signatures of antibodies raised in mice after sublingual immunization with a recombinant form of the P1 (aka AgI/II, PAc) adhesin (P139-512) of Streptococcus mutans, a major etiological agent of dental caries. Sublingual administration of P139-512 in combination with the mucosal adjuvant LTK4R (a derivative of heat-labile LT toxin) induced strong and long-lasting systemic and mucosal immune responses. Incorporation of the adjuvant resulted in an enhancement of the anti-adhesive and anti-colonization activity against S. mutans as evaluated both under in vitro and in vivo conditions. Incorporation of the adjuvant to the vaccine formulation also changed the epitope specificity of the induced antibodies as determined by immunological signatures of sera collected from vaccinated mice. Use of a peptide microarray library led to the identification of peptide targets recognized by antibodies in serum samples with enhanced anti-adhesive effects. Altogether, the results presented herein showed that the sublingual administration of a P1-based subunit vaccine represents a promising approach for the prevention of dental caries caused by S. mutans. In addition, the present study disclosed the role of adjuvants on the epitope specificity and functionality of antibodies raised by subunit vaccines.
AB - In this study, we evaluated the immunogenicity, protective efficacy and peptide-based immune signatures of antibodies raised in mice after sublingual immunization with a recombinant form of the P1 (aka AgI/II, PAc) adhesin (P139-512) of Streptococcus mutans, a major etiological agent of dental caries. Sublingual administration of P139-512 in combination with the mucosal adjuvant LTK4R (a derivative of heat-labile LT toxin) induced strong and long-lasting systemic and mucosal immune responses. Incorporation of the adjuvant resulted in an enhancement of the anti-adhesive and anti-colonization activity against S. mutans as evaluated both under in vitro and in vivo conditions. Incorporation of the adjuvant to the vaccine formulation also changed the epitope specificity of the induced antibodies as determined by immunological signatures of sera collected from vaccinated mice. Use of a peptide microarray library led to the identification of peptide targets recognized by antibodies in serum samples with enhanced anti-adhesive effects. Altogether, the results presented herein showed that the sublingual administration of a P1-based subunit vaccine represents a promising approach for the prevention of dental caries caused by S. mutans. In addition, the present study disclosed the role of adjuvants on the epitope specificity and functionality of antibodies raised by subunit vaccines.
KW - Anti-caries vaccine
KW - Epitope specificity
KW - Immunosignature
KW - Peptide microarray
KW - Streptococcus mutans
KW - Sublingual immunization
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U2 - 10.1016/j.vaccine.2017.11.007
DO - 10.1016/j.vaccine.2017.11.007
M3 - Article
C2 - 29146379
AN - SCOPUS:85034581924
SN - 0264-410X
VL - 35
SP - 7273
EP - 7282
JO - Vaccine
JF - Vaccine
IS - 52
ER -