An Intranasally Delivered Toll-Like Receptor 7 Agonist Elicits Robust Systemic and Mucosal Responses to Norwalk Virus-Like Particles

Velasquez, Lissette S.; Hjelm, Brooke E.; Arntzen, Charles J.; Herbst-Kralovetz, Melissa M.

doi:10.1128/cvi.00230-10

Cited by 44 publications

(58 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19,20 Nasal and oral routes of administration are particularly intriguing because they are known to induce immune responses at the delivery site, as well as distal mucosal sites, and provide an easy delivery route for human vaccinations. 1,3,5,11,13,14,19,20,[25][26][27] Oral delivery has been shown to be a safe delivery route, however one caveat is that oral vaccination requires a high antigen dose in order to achieve immunogenicity. 11,25,26 The nasal vaccination route has been significantly associated with Bell's palsy following co-delivery with E. coli enterotoxin; likewise, cholera toxin has been shown to transport to the central nervous system via toxin-specific receptors.…”

Section: Tlr7 and 9 Agonists Are Highly Effective Mucosal Adjuvants Fmentioning

confidence: 99%

“…Poor immunogenicity of non-replicating subunit vaccines, however, can be overcome by the addition (or co-delivery) of potent adjuvants. [1][2][3][4]6,7,9,[13][14][15][16][17][18][19] One particularly potent group of molecules that can be exploited as mucosal adjuvants are toll-like receptor (TLR) agonists. 1,3,[14][15][16][17][19][20][21][22][23][24] TLRs are pattern recognition receptors (PRRs) of the innate immune system that have been shown to exhibit tissue or mucosa-specific expression patterns.…”

mentioning

confidence: 99%

“…16,19,21,22,24 These TLR agonists, or PAMP, include bacterial ligands, virus-specific ribonucleotide motifs (i.e., dsRNA), and imidazoquinoline compounds and all are currently studied as adjuvants. [1][2][3][4]6,[14][15][16][17][18][19] We have previously published results demonstrating that intranasal co-delivery with gardiquimod (GARD; TLR7 agonist) and resiquimod (R848; TLR7/8 agonist) along with Norwalk virus (NV) VLPs can elicit equivalent immune responses relative to VLPs co-delivered with cholera toxin (CT).…”

mentioning

confidence: 99%

See 2 more Smart Citations

TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines

Hjelm

Kilbourne

Herbst-Kralovetz

2013

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Section: Tlr7 and 9 Agonists Are Highly Effective Mucosal Adjuvants Fmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines

Hjelm

Kilbourne

Herbst-Kralovetz

2013

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…Many studies have investigated these abilities and ascribed immune boosting response to one, other or both qualities. 26 Mucosal adjuvants that have been tested for intranasal vaccine delivery including: MF59 emulsion (containing squalene oil, the surfactants Span 85 and Tween 80 and citrate buffer), 105,106 lipopolysaccharide, 84,107 TLR agonists, 41,108,109 chitosan, 110 trimethylchitosan, 91,110 bacterial outer membrane protein 111 and cholera toxin 112 or heat-labile enterotoxin (LT) from E.coli. 113 Some side effects have been found with the use of bacterial toxin when given intranasally, including Bell's palsy (Facial paralysis) and other adverse events related to disorders of the facial nerves.…”

Section: Adjuvantsmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

View full text Add to dashboard Cite

Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...

show abstract

“…35 Superior to oral administration, intranasal immunization of VLPs without an adjuvant resulted in significantly higher immune responses. 36 An addition of adjuvants, such as the mutant Escherichia coli heat-labile toxin LT(R192G) 36 and a dry powder formulation (GelVac) of an inert in situ gelling polysaccharide (GelSite) extracted from Aloe vera, 37 further enhanced the immune responses.…”

Section: Preclinical Studies Of Nov Vaccinementioning

confidence: 99%