Intranasal booster vaccination against diphtheria and tetanus in man

Aggerbeck, Henrik; Gizurarson, Sveinbjörn; Wantzin, Jørgen; Heron, Iver

doi:10.1016/s0264-410x(96)00175-2

Cited by 51 publications

(20 citation statements)

References 25 publications

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“…In addition, we demonstrated that tracheal immunization of piglets with the rTbp B/chitosan formulation induces both serum and mucosal immune responses. These findings are similar to those of previous reports [1,9,17,18,27,28]. The chitosan microparticles showed excellent loading and release characteristics for the protein vaccine [27], which indicates that these microparticles can be used for multiple vaccines.…”

Section: Elisasupporting

confidence: 91%

Stimulation of Mucosal and Systemic Antibody Responses against Recombinant Transferrin-binding Protein B of Actinobacillus pleuropneumoniae with Chitosan after Tracheal Administration in Piglets

Kim

Lee

2007

The Journal of Veterinary Medical Science

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ABSTRACT. This study evaluated the suitability of using a chitosan formulation as an adjuvant to enhance both the mucosal and systemic immune responses against recombinant transferrin-binding protein B (rTbp B) of Actinobacillus pleuropneumoniae via direct tracheal administration. The chitosan formulation was found to enhance mucosal immune response, as measured by the secretory IgA level in lung lavage fluid and lung homogenate extracts, and systemic immune response, as measured by the serum IgG level. KEY WORDS: Actinobacillus pleuropneumoniae, chitosan, transferrin-binding protein.

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Section: Elisasupporting

confidence: 91%

Stimulation of Mucosal and Systemic Antibody Responses against Recombinant Transferrin-binding Protein B of Actinobacillus pleuropneumoniae with Chitosan after Tracheal Administration in Piglets

Kim

Lee

2007

The Journal of Veterinary Medical Science

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“…Various studies have confirmed the potential for intranasal immunization of humans with nonreplicating vaccines against a wide range of bacterial pathogens (5,6,9,10,12,14), including C. diphtheriae (1). Furthermore, intranasal immunization appears to offer the advantage of inducing combined systemic and secretory immunity, including at diverse mucosal sites, on May 11, 2018 by guest http://iai.asm.org/ such as the lung and genital tract (4,11,21,22).…”

Section: Discussionmentioning

confidence: 99%

“…Various human studies have reported nasal delivery of nonreplicating antigens from Shigella (9), diphtheria and tetanus toxoids (1), cholera toxin B subunit (4,21), Neisseria meningitidis (10,12), Pseudomonas (14), and Bordetella pertussis (5,6). However, no study has reported the induction of immunity that would satisfy established vaccine-licensing criteria.…”

mentioning

confidence: 99%

“…However, no study has reported the induction of immunity that would satisfy established vaccine-licensing criteria. Furthermore, reported secretory immunoglobulin A (sIgA) responses in mucosal secretions vary among subjects and anatomical sites (11), and intranasal diphtheria toxoid in alum induced significant side effects (1). Thus, a delivery system that can effectively induce both systemic and disseminated mucosal responses to nasally delivered nonreplicating antigens without inducing significant side effects remains a highly desirable goal.…”

mentioning

confidence: 99%

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Protective Levels of Diphtheria-Neutralizing Antibody Induced in Healthy Volunteers by Unilateral Priming-Boosting Intranasal Immunization Associated with Restricted Ipsilateral Mucosal Secretory Immunoglobulin A

et al. 2003

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Subunit intranasal vaccines offer the prospect of inducing combined systemic-mucosal immunity against mucosally transmitted infections such as human immunodeficiency virus. However, although human studies have demonstrated the induction of active immunity, secretory immunoglobulin A (sIgA) responses are variable, and no study has demonstrated protection by accepted vaccine-licensing criteria as measured by direct toxin-neutralizing activity. Using the genetically inactivated mutant diphtheria toxoid CRM 197 in a bioadhesive polycationic polysaccharide chitosan delivery system, we found that a single nasal immunization was well tolerated and boosted antitoxin neutralizing activity in healthy volunteers, which could be further boosted by a second immunization. The neutralizing activity far exceeded accepted protective levels and was equivalent to that induced by standard intramuscular vaccine and significantly greater than intranasal immunization with CRM 197 in the absence of chitosan. A striking but unexpected observation was that although unilateral intranasal immunization induced circulating antitoxin antibody-secreting cells, a nasal antitoxin sIgA response was seen only after the second immunization and only in the vaccinated nostril. If these data are reproduced in larger studies, an intranasal diphtheria vaccine based on CRM 197 -chitosan could be rapidly licensed for human use. However, a restricted sIgA response suggests that care must be taken in the priming-boosting strategy and clinical sampling techniques when evaluating such vaccines for the induction of local mucosal immunity.In murine models of immunization, the nasal route appears to have the advantage of inducing both a systemic and a disseminated mucosal response, making it highly attractive for the delivery of vaccines against mucosally transmitted infections. Various human studies have reported nasal delivery of nonreplicating antigens from Shigella (9), diphtheria and tetanus toxoids (1), cholera toxin B subunit (4, 21), Neisseria meningitidis (10, 12), Pseudomonas (14), and Bordetella pertussis (5, 6). However, no study has reported the induction of immunity that would satisfy established vaccine-licensing criteria. Furthermore, reported secretory immunoglobulin A (sIgA) responses in mucosal secretions vary among subjects and anatomical sites (11), and intranasal diphtheria toxoid in alum induced significant side effects (1). Thus, a delivery system that can effectively induce both systemic and disseminated mucosal responses to nasally delivered nonreplicating antigens without inducing significant side effects remains a highly desirable goal.The mutant diphtheria toxin CRM 197 contains an inactivating glycine-to-glutamic acid substitution at position 52 of the enzymatic A subunit and is widely used in humans as a licensed polysaccharide antigen carrier. CRM 197 is inherently nontoxic and does not require chemical inactivation. However, low-dose (0.18%) formaldehyde treatment enhances its immunogenicity for intranasal immunization of mice an...

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“…However, most pathogens gain access to their hosts via the mucosal surfaces (Aggerbeck et al, 1997;De Magistris, 2006). It is therefore important to provide an immunization by mucosal routes and it may be more effective at inducing protective immunity against mucosal pathogens at their sites of entry (Saatçi & Bozkır, 2003).…”

Section: Introductionmentioning

confidence: 99%

Preparation andin vitro/in vivoevaluation of mucosal adjuvantin situforming gels with diphtheria toxoid

2014

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Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model active substance and their intranasal administration have been conducted in this study. The objective of mucosal vaccination is to stimulate both systemic and mucosal immune responses. In situ gel formulations were prepared by using, in different ratios, mixtures of Poloxamer 407 and Poloxamer 188 polymers, which gelate in a temperature-dependent manner, and mucoadhesive polymers carbopol 934, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or chitosan. Following pre-formulation studies, F1, F2, F3, F4, F5, F6 and F7 formulations, which gelate at intervals and temperatures in accordance with nasal temperatures, were subjected to more comprehensive studies. For this purpose, organoleptic characteristics of the formulations were identified, their pH and mucoadhesive potencies were measured and rheological behaviors were characterized. Calculated amounts of diphtheria toxoid were added to formulations after optimization of formulations was achieved, and assay and in vitro release studies were carried out. Formulations coded F3 and F7 were considered to be superior to other formulations given the in vitro test results. Therefore, these formulations were tested in guinea pigs to determine immune responses, which they would produce following intranasal and subcutaneous administration. Absorbance values of ELISA tests and antibody neutralization test showed that formulations coded F3 and F7 were unable to stimulate adequate systemic immune response when either of the formulations was administered alone intranasally, whereas F7 resulted in significantly increased neutralizing antibody titers with intranasal administration as a booster dose following subcutaneous administration. KeywordsAdjuvant, diphtheria toxoid, in situ gel formulations, intranasal delivery, mucosal immune History

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Intranasal booster vaccination against diphtheria and tetanus in man

Cited by 51 publications

References 25 publications

Stimulation of Mucosal and Systemic Antibody Responses against Recombinant Transferrin-binding Protein B of Actinobacillus pleuropneumoniae with Chitosan after Tracheal Administration in Piglets

Stimulation of Mucosal and Systemic Antibody Responses against Recombinant Transferrin-binding Protein B of Actinobacillus pleuropneumoniae with Chitosan after Tracheal Administration in Piglets

Protective Levels of Diphtheria-Neutralizing Antibody Induced in Healthy Volunteers by Unilateral Priming-Boosting Intranasal Immunization Associated with Restricted Ipsilateral Mucosal Secretory Immunoglobulin A

Preparation andin vitro/in vivoevaluation of mucosal adjuvantin situforming gels with diphtheria toxoid

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