Use of the Inactivated Intranasal Influenza Vaccine and the Risk of Bell's Palsy in Switzerland

Mütsch, Margot; Zhou, Wen; Rhodes, Philip; Bopp, Matthias; Chen, Robert T.; Linder, Thomas; Spyr, Christian; Steffen, Robert P.

doi:10.1056/nejmoa030595

Cited by 812 publications

(530 citation statements)

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“…This is particularly true for mucosal immunization where CT and LT have been shown to undergo retrograde transport along olfactory nerves to olfactory bulbs in the brains of mice immunized via the intranasal route (reviewed in reference 3). In humans, severe adverse reactions including Bell's palsy have been reported following intranasal immunization with LT (24,31). These concerns are perhaps less relevant for skin delivery and are likely to be site and route specific due to the proximity of key neurological pathways to the site of antigen/adjuvant application at the nasal mucosa.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous Immunization with Cross-Reacting Material CRM ₁₉₇ of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

et al. 2008

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Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM 197 ) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM 197 significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM 197 alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM 197 protein. These findings highlight the promising prospect of using booster administrations of CRM 197 via the transcutaneous route to establish good herd immunity against diphtheria.

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Section: Discussionmentioning

confidence: 99%

Transcutaneous Immunization with Cross-Reacting Material CRM ₁₉₇ of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

et al. 2008

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“…The IN vaccination route was successful when used in humans against the influenza virus. However, the risk of Bell's palsy [27] was reported when this type of vaccine was applied in combination with E. coli toxin.…”

Section: Discussionmentioning

confidence: 99%

Intradermal DNA vaccination in ear pinnae is an efficient route to protect cats against rabies virus

et al. 2008

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-A DNA vaccine against rabies (pGQH) was administrated to cats in order to examine different administration routes. Four groups of three cats each were inoculated with pGQH as follows: group A, intramuscularly (IM), 100 µg; group B, intranasally (IN), 100 µg; group C, intradermally into ear pinnae (ID-EP), 100 µg, and group D, IM, 200 µL of phosphate buffer solution (PBS) alone (control group). Blood was drawn on days 0, 30, 60, 90, 120, 150, and 180. Groups A, B, and C received a booster on day 30. At day 200 all animals were challenged. A passive transfer of cat sera, as well as a viral challenge, was performed in mice. The results displayed that neutralizing antibody titers were higher in cats of group C (ID-EP) showing high early titers (> 2 IU) and the highest titer was on day 120 (> 14 IU). In group B (IN), two out of three cats seroconverted on day 30 (> 0.5 IU), the third cat seroconverted until day 60 (> 0.5 IU). In contrast, the lowest levels of neutralizing antibodies were detected in group A (IM). The control group showed no anti-rabies antibodies. Groups A (IM) and D (control) succumbed after lethal challenge. All animals from the ID-EP group (C) survived, only one individual from the IN (B) group died. Mice that received cat sera from ID-EP, IM, and IN groups survived and were protected (30/30 survivors). Mice groups that received pre-immunization sera from cats were not protected (0/30 survivors). This study demonstrates that pGQH immunization was successful when it was administrated ID-EP, and acceptable through the IN route. The IM route, however, was not effective in cats. For vaccination, the IN route seems attractive due to its accessibility for application, but it seems to activate seroconversion slowly. The best route to promote anti-rabies antibody titers was the ID-EP route. This practical and efficient route should be further studied.rabies / DNA vaccine / intradermal into ear pinna / intranasal / cats

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“…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. [114][115][116] It has been suggested that the central nervous system was involved in the palsy as the bacterial toxin was re-directed into the brain. 115,117 Thus, the use of LT as vaccine adjuvant is no longer recommended.…”

Section: Adjuvantsmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

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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...

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Use of the Inactivated Intranasal Influenza Vaccine and the Risk of Bell's Palsy in Switzerland

Abstract: This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell's palsy. This vaccine is no longer in clinical use.

Cited by 812 publications

References 26 publications

Transcutaneous Immunization with Cross-Reacting Material CRM ₁₉₇ of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

Transcutaneous Immunization with Cross-Reacting Material CRM ₁₉₇ of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

Intradermal DNA vaccination in ear pinnae is an efficient route to protect cats against rabies virus

Current prospects and future challenges for nasal vaccine delivery

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Use of the Inactivated Intranasal Influenza Vaccine and the Risk of Bell's Palsy in Switzerland

Abstract: This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell's palsy. This vaccine is no longer in clinical use.

Cited by 812 publications

References 26 publications

Transcutaneous Immunization with Cross-Reacting Material CRM 197 of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

Transcutaneous Immunization with Cross-Reacting Material CRM 197 of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

Intradermal DNA vaccination in ear pinnae is an efficient route to protect cats against rabies virus

Current prospects and future challenges for nasal vaccine delivery

Contact Info

Product

Resources

About

Transcutaneous Immunization with Cross-Reacting Material CRM ₁₉₇ of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine

Transcutaneous Immunization with Cross-Reacting Material CRM ₁₉₇ of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine