Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: A phase I study

Abstract

Japanese Red Cedar (JRC) pollen induced allergy affects one third of Japanese and the development of effective therapies remains an unachieved challenge. We designed a DNA vaccine encoding CryJ2 allergen from the JRC pollen and Lysosomal Associated Membrane Protein 1 (LAMP-1) to treat JRC allergy. These Phase IA and IB trials assessed safety and immunological effects of the investigational CryJ2-LAMP DNA vaccine in both non-sensitive and sensitive Japanese expatriates living in Honolulu, Hawaii. In the Phase IA trial, 6 JRC non-sensitive subjects and 9 JRC and/or Mountain Cedar (MC) sensitive subjects were given 4 vaccine doses (each 4mg/1ml) intramuscularly (IM) at 14-day intervals. Nine JRC and/or MC sensitive subjects were given 4 doses (2 mg/0.5 ml) IM at 14-day intervals. The safety and functional biomarkers were followed for 132 d. Following this, 17 of 24 subjects were recruited into the IB trial and received one booster dose (2 mg/0.5 ml) IM approximately 300 d after the first vaccination dose to which they were randomized in the first phase of the trial. All safety endpoints were met and all subjects tolerated CryJ2-LAMP vaccinations well. At the end of the IA trial, 10 out of 12 JRC sensitive and 6 out of 11 MC sensitive subjects experienced skin test negative conversion, possibly related to the CryJ2-LAMP vaccinations. Collectively, these data suggested that the CryJ2-LAMP DNA vaccine is safe and may be immunologically effective in treating JRC induced allergy.

DNA and mRNA vaccination against allergies

“…Interestingly, a substantial number of prick test conversions from positive to negative were also noted for unrelated allergens pointing to a possible bystander suppressive effect provided by T helper cells . Specific IgE titers remained unchanged upon immunization with the Cry j 2‐LAMP vaccine and unlike in the preceding mouse study, only a marginal increase in specific IgG was noted …”

“…Immunizations were well tolerated by all participants. Interestingly, 130 days after the 4th immunization 10 of 12 patients sensitized to Japanese red cedar and six of 11 patients sensitized to mountain cedar displayed a conversion of skin test from positive to negative . However, as skin prick tests at the time‐point of enrollment and at the study end‐point were performed using allergen extracts, it is difficult to assess whether treatment induced any Cry j 2‐specific immunological effects.…”

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

“…The current anti‐allergy DNA molecules tested in phase I/II were optimized for the MHC‐II presentation by the fusion with sequence encoding lysosomal‐associated membrane protein (LAMP) (Table 4). Conventional intramuscular administration of cedar pollen allergen Cry j 2‐LAMP DNA demonstrated the safety of the treatment in Japanese red cedar/mountain cedar‐sensitized patients . Conversion of some cedar pollen‐specific prick tests from positive to negative was observed, and similar results were also obtained for unrelated allergens, suggesting a possible bystander suppressive effect.…”

Next generation immunotherapy for tree pollen allergies

“…109 In a Phase IA and IB study, the safety and immunological effects of the CryJ2-LAMP DNA vaccine was evaluated in six non-atopic and eighteen JRC-and/or Mountain Cedar (MC)atopic Japanese expatriates living in Hawaii. 110 This is to our knowledge the first clinical trial for treating allergies with a DNA vaccine. The CryJ2-LAMP vaccine was well tolerated by both non-atopic and JRC-and/or MC-atopic subjects in a biweekly four-dose intramuscular immunization regimen (4mg or 2mg plasmid DNA per injection) and no severe adverse events were found.…”

“…The majority of JRC and/or MC atopic subjects experienced negative conversion of skin reaction against the JRC or MC extract and the negative skin conversion was maintained through the end of the trial in most subjects. 110 There were several limits in this trial, such as small study size, lack of placebo control, and lack of JRC and/or MC pollen exposure. However, data from this study of applying DNA vaccines in allergies indicate that DNA vaccine might be immunologically effective as a therapeutic for tree pollen allergies.…”