Preventing aspergillosis through immunization

Aspergillus fumigatus. Photo courtesy of
David Gregory and Debbie Marshall

Cara N. Wilder, Ph.D.

Over the last 20 years, Aspergillus fumigatus has become one of the most frequent causes of invasive fungal infection in immunologically compromised patients. This infection, termed aspergillosis, is associated with a wide spectrum of symptoms, including allergic reactions, organ failure, and lung infection. In most patients, A. fumigatus predominantly affects the lungs, resulting in an often fatal illness termed invasive pulmonary aspergillosis (IPA).

Current therapies for aspergillosis include treatment with antifungal drugs such as Amphotericin B or Triazole medications (Voriconazole, Posaconazole, Itraconazole). Unfortunately, these therapies have had limited success in treating IPA, and are often associated with serious toxicities. This is further compounded by the growing number A. fumigatus strains that have developed resistance against antifungal drugs, thus making the eradication of aspergillosis increasing more difficult. In response to these concerns, many research laboratories have focused their efforts on the development of new strategies targeted toward the prevention and treatment of such infections.

In one vaccine discovery program, Ito et al. used an immunochemical and mass spectrometric approach to identify an antigenic target for the development of a candidate vaccine that provides immunization against A. fumigatus. Following nasopulmonary inoculation of immunocompetent mice with viable A. fumigatus conida, Asp f 3 was identified as a potential antigenic target based on immunodominance during infection. Upon the analysis of this allergen, it was determined that subcutaneous immunization with full-length and truncated recombinant Asp f 3 offered protection against A. fumigatus infection. This was further confirmed following the examination of the lungs of vaccinated survivors, which were deemed free of hyphae and exhibited minimal infiltration of mononuclear cells. Overall, the findings from this study indicate that recombinant Asp f 3 is an effective immunogen and promising candidate for the development of a novel vaccine to prevent aspergillosis.



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