Sublingual immunization with the phosphate‐binding‐protein (PstS) reduces oral colonization by Streptococcus mutans

Abstract

Bacterial ATP-binding cassette (ABC) transporters play a crucial role in the physiology and pathogenicity of different bacterial species. Components of ABC transporters have also been tested as target antigens for the development of vaccines against different bacterial species, such as those belonging to the Streptococcus genus. Streptococcus mutans is the etiological agent of dental caries, and previous studies have demonstrated that deletion of the gene encoding PstS, the substrate-binding component of the phosphate uptake system (Pst), reduced the adherence of the bacteria to abiotic surfaces. In the current study, we generated a recombinant form of the S. mutans PstS protein (rPstS) with preserved structural features, and we evaluated the induction of antibody responses in mice after sublingual mucosal immunization with a formulation containing the recombinant protein and an adjuvant derived from the heat-labile toxin from enterotoxigenic Escherichia coli strains. Mice immunized with rPstS exhibited systemic and secreted antibody responses, measured by the number of immunoglobulin A-secreting cells in draining lymph nodes. Serum antibodies raised in mice immunized with rPstS interfered with the adhesion of bacteria to the oral cavity of naive mice challenged with S. mutans. Similarly, mice actively immunized with rPstS were partially protected from oral colonization after challenge with the S. mutans NG8 strain. Therefore, our results indicate that S. mutans PstS is a potential target antigen capable of inducing specific and protective antibody responses after sublingual administration. Overall, these observations raise interesting perspectives for the development of vaccines to prevent dental caries.

Dental caries vaccine: are we there yet?

“…Recently, a vaccine trial in mice using LT derivative (detoxified) as an adjuvant with the subunit of Pi 39‐512 and PstS protein has also been shown to elicit antigen‐specific antibody production and a reduction in the adherence of Strep. mutans (Ferreira et al ; Batista et al ).…”

“…First, to search for new target virulence genes or antigenic proteins, develop vaccines, use the best historically proved adjuvant and administration technique and enhance further using nanotechnology. For example, Ferreira et al () studied a completely new protein, PstS, which showed promising results. Second, existing best‐proved animal trial vaccines can be improved to the required level.…”

“…Recently, a vaccine trial in mice using LT derivative (detoxified) as an adjuvant with the subunit of Pi 39-512 and PstS protein has also been shown to elicit antigen-specific antibody production and a reduction in the adherence of Strep. mutans (Ferreira et al 2016;Batista et al 2017). Yang et al (2017) have also shown that a monomeric vaccine, KFD2-rPAc, which contains an alanine-rich to proline-rich region fragment of PAc from Strep.…”

“…Fewer studies have researched enolase (Dinis et al 2009(Dinis et al , 2011. In recent years, a vaccine has been developed using phosphate-binding-protein (Pst system) which also facilitates adhesion to abiotic surfaces (Luz et al 2012;Ferreira et al 2016). All these proteins have antigenic properties and can, therefore, elicit specific antibodies which are known to block the particular function of the virulence factors (Lehner et al 1980;Smith and Lehner 1981).…”

Novas abordagens vacinais contra <i>Streptococcus mutans</i>.

“…Um trabalho publicado em 2016 por nosso grupo de pesquisa, demostrou que a imunização sublingual de camundongos BALB/c utilizando como antígeno modelo uma proteína captadora de fosfato do sistema ABC de S. mutans, a proteína PstS em combinação ou não com a enterotoxina mutante LTK4R, foi capaz de estimular a produção de anticorpos sistêmicos e também ativar células secretoras de IgA no baço e linfonodos cervicais. Além disso, foi observado que os anticorpos gerados após o regime vacinal adotado foram eficientes em interferir na capacidade de colonização oral por S. mutans(59).…”