Trained Immunity Based-Vaccines as a Prophylactic Strategy in Common Variable Immunodeficiency. A Proof of Concept Study

Background. A major concern in the care of common variable immunodeficiency (CVID) patients is the persistence of subclinical or recurrent respiratory tract infections (RRTI) despite adequate trough IgG levels, which impacts the quality of life (QoL) and morbidity. Therefore, the development of new approaches to prevent and treat infection, especially RRTI, is necessary. Objectives. We conducted a clinical observational study from May, 2016 to December, 2017 in 20 CVID patients; ten of these patients had a history of RRTI and received the polybacterial preparation MV130, a trained immunity-based vaccine (TIbV) to assess its impact on their QoL and prognosis. Methods. Subjects with RRTI received MV130 for 3 months and were followed up to 12 months after initiation of the treatment. The primary endpoint was a reduction in RRTI at the end of the study. We analyzed the pharmacoeconomic impact on the RRTI group before and after immunotherapy by estimating the direct and indirect costs, and assessed CVID-QoL and cytokine profile. Specific antibody responses to the bacteria contained in MV130 were measured. Results. The RRTI-group treated with TIbV MV130 showed a significant decrease in infection rate (p= 0.006) throughout the 12 months after initiation of the treatment. A decrease in antibiotic use and unscheduled outpatient visits was observed (p= 0.005 andp= 0.002, respectively). Significant increases in anti-pneumococcus and anti-MV130 IgA antibodies (p= 0.039 both) were detected after 12 months of MV130. Regarding the CVID QoL questionnaire, an overall decrease in the score by more than 50% was observed (p< 0.05) which demonstrated that patients experienced an improvement in their QoL. The pharmacoeconomic analysis showed that the real annual direct costs decreased up to 4 times per patient with the prophylactic intervention (p= 0.005). Conclusion. The sublingual administration of the TIbV MV130 significantly reduced the rate of respiratory infections, antibiotic use and unscheduled visits, while increasing specific IgA responses in CVID patients. Additionally, the CVID population felt that their QoL was improved, and a decrease in expenses derived from health care was predicted.