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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Vaccine; v. 35, n. 52, p. 7273-7282, DEC 19 2017.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 15/15562-0 - Caracterização da imunoassinatura dos anticorpos produzidos depois da imunização de mucosa em camundongos contra a cárie dental humana
• Beneficiário: Milene Tavares Batista
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 12/51189-3 - Bacillus subtilis como plataforma para o desenvolvimento de vacinas de mucosa contra a cárie dental humana
• Beneficiário: Milene Tavares Batista
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/06671-4 - Novos antígenos vacinais para o controle de Streptococcus mutans
• Beneficiário: Rita de Cássia Café Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular