A sublingual nanofiber vaccine to prevent urinary tract infections

Abstract

Urinary tract infections (UTIs) are a major public health problem affecting millions of individuals each year. Recurrent UTIs are managed by long-term antibiotic use, making the alarming rise of antibiotic resistance a substantial threat to future UTI treatment. Extended antibiotic regimens may also have adverse effects on the microbiome. Here, we report the use of a supramolecular vaccine to provide long-term protection against uropathogenic Escherichia coli , which cause 80% of uncomplicated UTIs. We designed mucus-penetrating peptide-polymer nanofibers to enable sublingual (under the tongue) vaccine delivery and elicit antibody responses systemically and in the urogenital tract. In a mouse model of UTI, we demonstrate equivalent efficacy to high-dose oral antibiotics but with significantly less perturbation of the gut microbiome. We also formulate our vaccine as a rapid-dissolving sublingual tablet that raises response in mice and rabbits. Our approach represents a promising alternative to antibiotics for the treatment and prevention of UTIs.

Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles

“…They also have been formulated with adjuvants. [ 47,63,105,116,141,[143][144][145][146] Here, we have reviewed methods and techniques that enable incorporation of antigens into protein nanoparticle design. Chemical conjugation, including amine, thiol, and click chemistry and crosslinking, is an extensively used route that enables direct addition of antigens onto the surface of nanoparticles with high conjugation efficiency.…”

“…[ 100 ] Aside from oncoantigens, Q11 has been used for a wide variety of antigens including viral antigens such as HIV gp120 envelope glycoprotein [ 101,102 ] and self-antigens such as anti-TNF B cell epitopes. [ 103,104 ] When antigens were used in conjunction with T cell epitopes and adjuvants, such as STING and TLR9 agonists [ 105 ] or complement protein C3dg 104 , enhanced immunogenicity was seen in immunized mice. Q11 has been shown to be a versatile platform to display various antigens for different vaccine applications.…”

MV140 mucosal bacterial vaccine improves uropathogenic E. coli clearance in an experimental model of urinary tract infection

“…This is highly desirable to provide an efficient protection against pathogen invasion through mucosal tissues as shown for other whole-cell bacterial formulations (24)(25)(26). Recently, a sublingual vaccine with peptides derived from the UPEC strain CFT073 has been shown to be effective against an experimental challenge with this particular strain, although the efficacy of this vaccine against other UPEC strains remains to be evaluated (27).…”

Self-Assembling Allergen Vaccine Platform Raises Therapeutic Allergen-Specific IgG Responses without Induction of Systemic Allergic Responses

“…All peptides were synthesized using Fmoc solid-phase chemistry on a CEM Liberty Blue microwave-assisted synthesizer and purified with high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization−mass spectrometry (MALDI−MS), as previously reported. 31 Biotinylated peptides were synthesized on-resin by reacting Biotin-ONp (33755-53-2, Novabiochem) with amine-terminated peptides in a 3-fold excess overnight in dimethyl sulfoxide (DMSO). Alexafluor-647labeled peptides were synthesized on-resin by reacting 5 mg of Alexa Fluor 647 NHS Ester (Succinimidyl Ester) (ThermoFisher, A20006) with 0.05 mmol of amine-terminated peptide overnight in DMSO.…”

“…27 Q11 nanofibers are self-adjuvanting, although additional adjuvants and surface molecules can be included to tailor the immune response 28,29 or enable various routes of administration. 30,31 While the exact mechanism of Q11 nanofiber self-adjuvancy and immunogenicity remains to be elucidated, we have shown that these fiber immunogens are minimally inflammatory and elicit lower levels of inflammatory cytokine responses compared with other traditional adjuvants, such as alum. 32−34 Here we explore the use of this supramolecular nanofiber vaccine system as an allergen vaccine platform.…”