Phase 1 Evaluation of Intranasal Virosomal Influenza Vaccine with and without<i>Escherichia coli</i>Heat-Labile Toxin in Adult Volunteers

Glück, Ulrich; Gebbers, Jan‐Olaf; Glück, Reinhard

doi:10.1128/jvi.73.9.7780-7786.1999

Cited by 131 publications

(24 citation statements)

References 19 publications

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“…and IVAG routes under deep anesthesia 17–19. The following adjuvants were coadministered in combinations as mentioned in the Results section: Resiquimod (R‐848, 75 μg per dose; Huang Lisheng Pharmatec, China), heat‐labile enterotoxin (HLT,20 0.4 μg per dose; kindly provided by C. Gremion, Pevion Biotech, Bern, Switzerland) and CpG oligodeoxynucleotides 1826 (10 μg per dose; Coley Pharmaceutical Group, Wellesley, MA). Murine cells from blood, spleen, lymph nodes and genital tract were prepared as previously described 21.…”

Section: Methodsmentioning

confidence: 99%

Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus‐associated genital tumors

Decrausaz

Domingos-Pereira

Duc

et al. 2011

Intl Journal of Cancer

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Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE7 1 CD81 and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.Vaccination strategies that elicit cell-mediated immunity in the genital mucosa (GM) may be critical for protection against pathogens that use this mucosa as entry and replication site. This may be especially relevant in the case of genital human papillomavirus (HPV), as persistent infection with the high-risk types, most often HPV type 16 (HPV16), may lead to malignant diseases, including cervical cancer, 1 the second leading cause of cancer death in women worldwide.2 The available prophylactic vaccines prevent HPV infections through the induction of neutralizing antibodies, but they possess no therapeutic effects on already established HPV infections or associated lesions.3 Control of these lesions by cell-mediated immune responses is demonstrated by their increased prevalence when cell-mediated immunity is impaired [4][5][6] and by the finding that early infiltration of highly cytotoxic effector T cells in low-grade genital lesions appears to provide protection against tumor progression. 7 Thus, induction of cell-mediated immune responses against the HPV oncogenes (E6 and/or E7), which are implicated in initiation and maintenance of high-grade anogenital lesions, became an attractive approach, though with limited clinical success to date. 8 The most promising results [i.e., 47% regression of vulvar int...

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Section: Methodsmentioning

confidence: 99%

Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus‐associated genital tumors

Decrausaz

Domingos-Pereira

Duc

et al. 2011

Intl Journal of Cancer

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“…A causal relationship between the intranasally administered inactivatedinfluenza vaccine used in Switzerland and the incidence of Bell's palsy was formally established in a recent case-control study 96 . At this stage, the causes and pathogenesis of Bell's palsy remain unclear; however, because nLT has been shown to have proinflammatory properties and possible neurological toxicity 97 , the co-formulated nLT that is present in the inactivated-influenza vaccine is suspected to be the causative agent 98 . These findings highlight that the development of a safe mucosal adjuvant is crucial if progress is to be made towards a safe and effective mucosal vaccine.…”

Section: Recent Progress In Clinical Application Of Nasal Vaccinationmentioning

confidence: 99%

NALT- versus PEYER'S-patch-mediated mucosal immunity

2004

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Recent studies indicate that the mechanism of nasopharynx-associated lymphoid tissue (NALT) organogenesis is different from that of other lymphoid tissues. NALT has an important role in the induction of mucosal immune responses, including the generation of T helper 1 and T helper 2 cells, and IgA-committed B cells. Moreover, intranasal immunization can lead to the induction of antigen-specific protective immunity in both the mucosal and systemic immune compartments. Therefore, a greater understanding of the differences between NALT and other organized lymphoid tissues, such as Peyer's patches, should facilitate the development of nasal vaccines.

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“…Virosomes enable efficient induction of humoral and cellular responses and target dendritic cells [71][72][73][74][75][76]. They have been demonstrated to be efficient nasal delivery systems for several antigens, including DNA [75], and influenza [77,78] and HIV proteins [79].…”

Section: Particulate Delivery Systemsmentioning

confidence: 99%