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

Author(s)

Batista, Milene Tavares ^{[1, 2]} ; Ferreira, Ewerton Lucena ^[1] ; Pereira, Gisela de Souza ^[1] ; Stafford, Phillip ^[2] ; Nascimento Fabris Maeda, Denicar Lina ^[1] ; Rodrigues, Juliana Falcao ^[1] ; Brady, L. Jeannine ^[3] ; Johnston, Stephen Albert ^[2] ; de Souza Ferreira, Luis Carlos ^[1] ; Cafe Ferreira, Rita de Cassia ^[1]

Affiliation

^[1] Univ Sao Paulo, Biomed Sci Inst, Dept Microbiol, Ave Prof Lineu Prestes, 1374, BR-05508900 Sao Paulo, SP - Brazil

^[2] Arizona State Univ, Ctr Innovat Med, Biodesign Inst, Tempe, AZ - USA

^[3] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL - USA

• Document type: Journal article
• Source: Vaccine; v. 35, n. 52, p. 7273-7282, DEC 19 2017.
• Web of Science Citations: 2

Abstract

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 (P1(39-512)) of Streptococcus mutans, a major etiological agent of dental caries. Sublingual administration of P1(39-512) 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. (C) 2017 Published by Elsevier Ltd. (AU)

• FAPESP's process: 15/15562-0 - Characterization of the immunosignature of the antibodies produced after a mucosal vaccination strategies in mice against human dental caries
• Grantee: Milene Tavares Batista
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 12/51189-3 - Bacillus subtilis as a platform for mucosal vaccines development against human dental caries
• Grantee: Milene Tavares Batista
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/06671-4 - New vaccine antigens for the control of Streptococcus mutans
• Grantee: Rita de Cássia Café Ferreira
• Support Opportunities: Regular Research Grants