We are presenting two individuals with biallelic C-C chemokine receptor type 2 (CCR2) deficiency carrying the novel c.644C>T p.L215P variant, who presented with chronic respiratory symptoms during infancy and developed multiple diffuse cystic lesions during childhood.
The patients were diagnosed by means of whole exome sequencing and functional validation of the variant was performed in primary patient cells.
While size and extent of the cysts were stable over years, progressive lung function decline was noted in adolescence and adulthood respectively. The CCR2 p.L215P variant was found to be loss-of-expression and patient monocytes displayed a migration defect upon stimulation with the CCR2 ligand C-C motif ligand 2 (CCL2).
With a follow-up of up to 25 years, this report expands our understanding of lung disease in CCR2 deficiency and offers another monogenic cause of cystic lung disease. Early genetic diagnosis of affected individuals might allow potentially curative treatment by haematopoietic stem cell transplantation.
© 2025 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.

The oral mucosa is an attractive site for mucosal vaccination, however the thick squamous epithelium limits antigen uptake. Here we utilize a modified needle-free injector to deliver immunizations to the sublingual and buccal (SL/B) tissue of rhesus macaques. Needle-free SL/B vaccination with modified vaccinia Ankara (MVA) and a recombinant trimeric gp120 protein generates strong vaccine-specific IgG responses in serum as well as vaginal, rectal and salivary secretions. Vaccine-induced IgG responses show a remarkable breadth against gp70-V1V2 sequences from multiple clades of HIV-1. In contrast, topical SL/B immunizations generates minimal IgG responses. Following six intrarectal pathogenic SHIV-SF162P3 challenges, needle-free but not topical immunization results in a significant delay of acquisition of infection. Delay of infection correlates with non-neutralizing antibody effector function, Env-specific CD4+ T-cell responses, and gp120 V2 loop specific antibodies. These results demonstrate needle-free MVA/gp120 oral vaccination as a practical and effective route to induce protective immunity against HIV-1.