A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine

Bielinska, Anna U.; Чепурнов, А. А.; Landers, Jeffrey J.; Janczak, Katarzyna; Chepurnova, Tatiana S.; Luker, Gary D.; Baker, James R.

doi:10.1128/cvi.00440-07

Cited by 47 publications

(28 citation statements)

References 41 publications

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“…Studies with a prototype NE formulations showed that the NE can inactivate whole influenza virus and induce an immune response after nasal administration that protects mice from homologous influenza virus challenge (25). Similar protective immune responses were observed using the NE with either whole vaccinia virus (VV) (7) or purified antigens such as recombinant anthrax protective antigen (8). Immunization with recombinant HIV gp120 and NE adjuvant produced a Th1 immune response and neutralizing antibodies in mice (9).…”

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confidence: 65%

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

Hamouda

Sutcliffe

Ciotti

et al. 2011

Clin Vaccine Immunol

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confidence: 65%

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

Hamouda

Sutcliffe

Ciotti

et al. 2011

Clin Vaccine Immunol

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“…We have previously demonstrated protective immunity in a variety of antigen systems including influenza virus, recombinant anthrax protective antigen, HIV gp120, vaccinia virus, and hepatitis B surface antigen (HBsAg) in animal models, suggesting a possible utility of NE-based vaccines. (15)(16)(17)(18)(19) The successful use of NE-based vaccines, however, poses challenges. One such challenge is optimization of the platform for thermal stability and potency.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Stability and Nasal Delivery Systems for Immunization with Nanoemulsion-Based Vaccines

Makidon

Nigavekar

Bielinska

et al. 2010

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: Many infectious diseases that cause significant morbidity and mortality, especially in the developing world, could be preventable through vaccination. The effort to produce safe, thermally stable, and needlefree mucosal vaccines has become increasingly important for global health considerations. We have previously demonstrated that a thermally stable nanoemulsion, a mucosal adjuvant for needle-free nasal immunization, is safe and induces protective immunity with a variety of antigens, including recombinant protein. The successful use of nanoemulsion-based vaccines, however, poses numerous challenges. Among the challenges is optimization of the formulation to maintain thermal stability and potency and another is accuracy and efficiency of dispensing the vaccines to the nasal mucosa in the anterior and turbinate region of the nasal cavity or potentially to the nasopharynx-associated lymphoid tissue. Methods: We have examined the effects of different diluents [phosphate-buffered saline (PBS) and 0.9% NaCl] on the stability and potency of nanoemulsion-based vaccines. In addition, we have determined the efficiency of delivering them using commercially available nasal spray devices (Pfeiffer SAP-62602 multidose pump and the BD Hypak SCF 0.5 ml unit dose Accuspray TM ). Results: We report the stability and potency of PBS-diluted ovalbumin-nanomeulsion mixtures for up to 8 months and NaCl-diluted mixtures up to 6 months when stored at room temperature. Significant differences in spray characteristics including droplet size, spray angle, plume width, and ovality ratios were observed between the two pumps. Further, we have demonstrated that the nanoemulsion-based vaccines are not physically or chemically altered and retain potency following actuation with nasal spray devices. Using either device, the measured spray characteristics suggest deposition of nanoemulsion-based vaccines in inductive tissues located in the anterior region of the nasal cavity. Conclusions: The results of this study suggest that nanoemulsion-based vaccines do not require specially engineered delivery devices and support their potential use as nasopharyngeal vaccine adjuvants.

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“…NE-based vaccines formulated with various viral and bacteria-derived Ags and administered intranasally (i.n.) produced protective immunity to a variety of pathogens, including anthrax, vaccinia, HIV, influenza, and hepatitis B surface Ag (32)(33)(34)(35). Recently, we also demonstrated that W 80 5EC NE increases Ag uptake and trafficking by epithelial cells and DCs, resulting in both apoptosis and DC maturation (36,37).…”

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confidence: 97%

“…This NE adjuvant is simply an oil-in-water formulation of emulsified, highly refined soybean oil combined with nonionic and cationic surfactants and ethanol, and it is similar in size to many viruses that infect the nasal mucosa (32). Our studies (32)(33)(34) showed that nasal administration of the NE adjuvant mixed with Ag(s) induces robust mucosal and systemic Ab responses and unique Th-1-biased and Th-17-mediated cellular immunity without causing acute inflammation in the nasal mucosa. NE-based vaccines formulated with various viral and bacteria-derived Ags and administered intranasally (i.n.)…”

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confidence: 99%

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.

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A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine

Cited by 47 publications

References 41 publications

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

Characterization of Stability and Nasal Delivery Systems for Immunization with Nanoemulsion-Based Vaccines

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

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