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Is intralymphatic allergen-specific immunotherapy a safe and effective alternative to traditional allergen vaccination?

Principal investigator; Cardell, Lars-Olaf, , MD/PhD

Clinical speciality: Oto-rhino-laryngology

Phone: ++4640338231

Co-workers: Rolf Uddman, professor - Johan Kinhult, post doc - Ulf Höckerfelt, post doc

Allergen-specific immunotherapy is commonly used to treat patients with IgE-mediated allergic disorders like asthma and rhinitis. The current subcutaneous treatment protocol necessitates more than 50 physician-administrated injections/visits during 3-5 years. The fervent visits need to fulfill the treatment greatly limits availability of the therapy. A recent study suggests that direct intralymphatic, instead of subcutaneous injections, could yield faster beneficial results with lower allergen-doses and fewer injections. However, this new way of administrating the vaccine needs to be further evaluated before it can be used in clinical practice.

Purpose and aims
The aim of the project is to evaluate if intralymphatic allergen administration can provide a safe, effective and less time-consuming alternative to conventional subcutaneous allergy vaccination.

Study population
Patients with birch-pollen induced allergic rhinitis are recruited among the patients remitted to the Allergy unit at the department of Otorhinolaryngology at Malmö University Hospital.

Work plan
During winter 2009, 6 patients were recruited for an open intralymphatic pilot study. In autumn 2010, 16 patients were enrolled in a double-blind placebo-controlled study and thirty-four additional patients will be recruited during autumn 2011.

Study design
The proposal consists of six partly integrated phases. At visit 1, 5 and 6 patients undergo an extensive physical examination and various clinical and immunological tests. At visit 2-4, the patients receive intralymphatic administration of allergen.

Materials and Methods
Patients are treated with three intralymphatic injections of ALK Alutard (1,000 SQ-U Betula Verrucosa with an interval of 4 weeks). Pre- and post treatment, the patients are evaluated by nasal allergen provocation with symptom scoring, skin prick testing and measurements of pulmonary NO levels. Additionally, blood samples are collected and analyzed for IgE, leukocyte differentiation and various immunological parameters.

Preliminary data
So far, all patients given intralymphatic vaccination have completed the treatment without any severe adverse events and reported that the injections were virtually painless. Preliminary data suggest a reduction of allergen-specific IgE, a decrease in symptom scores after allergen challenge along with alterations in leukocyte phenotypes and immunological responses after completed treatment.

Intralymphatic immunotherapy will allow high therapeutic efficacy due to considerably reduced treatment dose and substantially shortened treatment duration. Combined with a good safety profile, this treatment will likely increase treatment compliance and reduce socioeconomic costs. By investigating the clinical, cellular and immunological effects of intralymphatic allergen-specific immunotherapy, we hope to in a near future will be able to able to use intralymphatic vaccination in the general clinical practice.

Link to project homepage: http://

5 recent original publications

Perez Vidakovics, Jendholm J, Mörgelin M, Månsson M, Larsson C, Cardell LO, Riesbeck K. B
Cell Activation by Outer Membrane Vesicles − A Novel Virulence Mechanism PLoS Pathogens
PLoS Pathogens . 2010; 15: ;6:e1000724

Månsson A, Cardell LO.
Role of atopic status in Toll-like receptor (TLR)7- and TLR9-mediated activation of human eosinophils.
J Leukoc Biol . 2009; 85: 719-27.

Zhang Y, Xu C-B, Cardell LO.
Long-term exposure to IL-1β enhances Toll-IL-1 receptor-mediated inflammatory signalling in murine airway hyperresponsiveness.
Eur Cytokine Netw. 2009; 20: 148-56

Månsson A, Fransson M, Adner M, Benson M, Uddman R, Björnsson S, Cardell LO
TTLR3 in Human Eosinophils: Functional Effects and Decreased Expression During Allergic Rhinitis.
Int Arch All Immun. 2009; in press: 100

Ekman AK, Fransson M, Rydberg C, Adner M, Cardell LO.
Nasal challenge with LPS stimulates the release of macrophage inflammatory protein 1alpha.
Int Arch Allergy Immunol. . 2009; 149: 154-160

Further publications here (new window)

Financing/year