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

Batista, Milene Tavares; Ferreira, Ewerton Lucena; Pereira, Gisela de Souza; Stafford, Phillip; Maeda, Denicar Lina Nascimento Fabris; Rodrigues, Juliana Falcão; Brady, L. Jeannine; Johnston, Stephen Albert; Ferreira, Luís Carlos de Souza; Ferreira, Rita de Cássia Café

doi:10.1016/j.vaccine.2017.11.007

Cited by 17 publications

(15 citation statements)

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“…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.…”

Section: Lessons Learned and Where Are We Today?mentioning

confidence: 99%

“…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 ).…”

Section: Lessons Learned and Where Are We Today?mentioning

confidence: 99%

“…As adjuvants, the use of enterotoxins from E. coli, Vibrio cholera and Salm. typhimurium have been successfully investigated in caries vaccines (Hajishengallis et al 1998;Saito et al 2001;Zhao et al 2011;Batista et al 2017). However, toxin-related adjuvants may cause adverse effects on intranasal administration, therefore, non-toxic derivatives of the labile-toxin (LTK4R) produced by enterotoxigenic E. coli have been investigated with promising results (Batista et al 2017).…”

Section: Routes Of Application and Adjuvantsmentioning

confidence: 99%

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Dental caries vaccine: are we there yet?

Patel

2020

Letters in Applied Microbiology

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Dental caries, caused by Streptococcus mutans, is a common infection. Caries vaccine has been under investigation for the last 40 years. Many in vitro and in vivo studies and some human clinical trials have determined many pertinent aspects regarding vaccine development. The virulence determinants of Strep. mutans, such as Ag I/II, responsible for adherence to surfaces, glucosyltransferase, responsible for the production of glucan, and the glucan‐binding protein, responsible for the attachment of glucan to surfaces, have been known to elicit an antigen‐specific immune response. It is also known that more than one antigen or a functional part of the genome responsible for these virulence determinants provide a better host response compared with the monogenic vaccine or complete genome of a specific antigen. To enhance the host response, the use of adjuvants has been studied and the routes of antigen administration have been investigated. In recent years, some promising vaccines such as pGJA‐P/VAX, LT derivative/Pi39‐512, KFD2‐rPAc and SBR/GBR‐CMV‐nirB have been developed and tested in animals. New virulence targets need to be explored. Multicentre collaborative studies and human clinical trials are required and some interest from funders and public health experts should be generated to overcome this hurdle. Significance and Impact of the Study Dental caries is an irreversible, multifactorial opportunistic infection. The treatment is costly, making it a public health problem. Despite many years of promising laboratory research, animal studies and clinical trials, there is no commercially available vaccine today. The research objectives have become more refined from lessons learnt over the years. Multigenic DNA/recombinant vaccines, using the best proved adjuvants with a delivery system for the nasal or sublingual route, should be developed and researched with multicentre collaborative efforts. In addition, new vaccine targets can be identified. To overcome the economic hurdle, funders and public health interest should be stimulated.

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Section: Lessons Learned and Where Are We Today?mentioning

confidence: 99%

Section: Lessons Learned and Where Are We Today?mentioning

confidence: 99%

Section: Routes Of Application and Adjuvantsmentioning

confidence: 99%

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Dental caries vaccine: are we there yet?

Patel

2020

Letters in Applied Microbiology

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“…Early investigations on the topic were excellently reviewed (Taubman and Nash, 2006). More recent studies have explored vaccination using a recombinant P1 adhesin antigen (Batista et al, 2017), a DNA-based vaccine against glucosyltransferases and surface proteins (Jiang et al, 2017), and a glycoconjugate vaccine based on rhamnan surface polysaccharides (St Michael et al, 2018). Unfortunately, past, present, and likely future, translational endeavors to move anti-caries vaccine research into clinical trials face significant regulatory and investment headwinds due to the fact that it is a non-life-threatening disease.…”

Section: Preventative Approaches In Developmentmentioning

confidence: 99%

Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?

Baker

Edlund

2019

Front. Microbiol.

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To compete in the relatively exposed oral cavity, resident microbes must avoid being replaced by newcomers. This selective constraint, coupled with pressure on the host to cultivate a beneficial microbiome, has rendered a commensal oral microbiota that displays colonization resistance, protecting the human host from invasive species, including pathogens. Rapid increases in carbohydrate consumption have disrupted the evolved homeostasis between the oral microbiota and dental health, reflected by the high prevalence of dental caries. Development of novel modalities to prevent caries has been the subject of a breadth of research. This mini review provides highlights of these endeavors and discusses the rationale and pitfalls behind the major avenues of approach. Despite efficacy, fluoride and other broad-spectrum interventions are unlikely to further reduce the incidence of dental caries. The most promising methodologies in development are those that exploit the exclusive nature of the healthy oral microbiome. Probiotics derived from the dental plaque of healthy individuals sharply antagonize cariogenic species, such as Streptococcus mutans. Meanwhile, targeted antimicrobials allow for the killing of specific pathogens, allowing reestablishment of a healthy microbiome, presumably with its protective effects. The oral microbiota manufactures a massive array of small molecules, some of which are correlated with health and are likely to antagonize pathogens. The prohibitive cost associated with sufficiently rigorous clinical trials, and the status of dental caries as a non-life-threatening condition will likely continue to impede the advancement of new therapeutics to market. Nevertheless, there is room for optimism, as it appears evolution may have already provided the best tools.

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“…BRERETON et al, 2011;BRAGA et al, 2014;BATISTA et al, 2017). Em estudos relacionados à resposta imunológica humoral induzida pela administração de LT e seus mutantes ou derivados atóxicos, a investigação da potência e modulação de resposta é limitada a determinação dos títulos e subclasses de anticorpos antígeno-específicos(HAAN et al, 1999; FRASER et al, 2003).…”

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Identificação de epítopos presentes na proteína e do vírus dengue tipo 2 (DENV2) capazes de gerar anticorpos neutralizantes sem a promoção da exacerbação da replicação viral.

Maeda¹,

Ferreira²

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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

Cited by 17 publications

References 62 publications

Dental caries vaccine: are we there yet?

Dental caries vaccine: are we there yet?

Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?

Identificação de epítopos presentes na proteína e do vírus dengue tipo 2 (DENV2) capazes de gerar anticorpos neutralizantes sem a promoção da exacerbação da replicação viral.

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