In a lung transplant recipient, phage therapy was associated with a T follicular helper cell response and production of neutralizing antibody.
Phage therapy with bacteriophages (viruses that infect bacteria) has undergone a resurgence due to rising antibiotic-resistant infections, particularly among immunocompromised patients. Although immune responses are known to develop against bacteriophages, how rapidly this outcome occurs and what effect it will have on therapeutic efficacy is not clear. Investigators studied samples from a bilateral lung transplant recipient with a multidrug-resistant Pseudomonas aeromonas pneumonia who had received an initial 2-week course of intravenous phage therapy followed by inhaled phage therapy upon relapse. Ultimately, the pneumonia resolved and the patient was discharged.
After the initiation of intravenous phage treatment, the number of activated circulating T follicular helper cells (Tfh) — which facilitate B cell differentiation and generation of high-affinity antibodies — peaked by day 14. These declined slightly after stopping intravenous phage treatment but rose again 1 week after inhaled phage therapy was initiated and were shown to be phage specific. Concurrently, phage-specific IgG-neutralizing antibodies increased beginning after 3 weeks of intravenous phage therapy and persisted during inhaled therapy.
- NOTE: These results are not unexpected, given that bacteriophages contain foreign protein, DNA, and RNA. However, the finding of a robust Tfh cell response with neutralizing antibody production against the phage is concerning. While this response did not lead to treatment failure, such an outcome may not be guaranteed in the future as phage therapy’s use expands — particularly in patients who are capable of a more-robust immune response.
- Dan JM et al. Development of host immune response to bacteriophage in a lung transplant recipient on adjunctive phage therapy for a multidrug resistant pneumonia. J Infect Dis 2022 Sep 9; [e-pub]. (https://doi.org/10.1093/infdis/jiac368. opens in new tab)
2. Molleston JM and Holtz LR. Fighting the wrong enemy: Antibacteriophage immunity in phage therapy. J Infect Dis 2022 Sep 9; [e-pub]. (https://doi.org/10.1093/infdis/jiac369. opens in new tab)
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