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

Abstract

<jats:p>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 and p = 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 &lt; 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.</jats:p>

Trained Immunity-Based Vaccine in B Cell Hematological Malignancies With Recurrent Infections: A New Therapeutic Approach

“…These results are one of the main strengths of this study, we believe it may be somehow underlying the mechanism of protection conferred by MV130 reducing the recurrence of infection in these patients. Furthermore, these data support a recently published report where patients with common variable immunodeficiency that received MV130 immunotherapy declined their rate of respiratory infections in parallel with an increase in MV130-specific IgA serum antibodies ( 26 ). The potential of MV130 to offer certain protection to infection by the recent SARS-CoV-2 virus in this population would also be interesting to explore.…”

“…According to health organizations advice for seeking new treatment alternatives against bacterial diseases, and to mitigate many factors to be considered when choosing empirical antibiotic, effective treatment for recurrent infections without side effects and bacterial resistance is necessary ( 29 ). Hence, TIbVs have been described useful in preventing recurrent respiratory infections, in both adults and pediatric populations and in the setting of primary immunodeficiency ( 26 , 30 , 31 ). Here, we report the beneficial effects of MV130, a mucosal polybacterial preparation, in a small cohort of HM patients as adjuvant or monotherapy for the prevention of recurrent respiratory infections.…”

“…In addition, clinical studies have pointed out trained immunity as a novel approach to enhance responses against infection and vaccination in the elderly and other vulnerable populations when innate immune cells display functional defects, such as decrease in the phagocytosis and cytokine production, and adaptive immune cells exhibit defective antibody production and/or a decline in naïve cell population ( 36 ). Certain bacterial preparations that have previously demonstrated clinical benefit reducing recurrent infections such as MV130, have been postulated as TIbVs for their ability to promote host resistance against a wide spectrum of pathogens ( 19 , 21 , 25 , 26 ). In this regard, we have not evaluated the ability of MV130 to induce trained immunity in the cohort of patients studied, but we have rather assessed an increase in antibody production.…”

“…, S. pneumoniae , S. epidermidis , S. aureus , M. catarrhalis , K. pneumoniae , and H. influenzae ) were determined in serum samples from blood collected before starting immunotherapy with MV130 and between 4 to 41 months after initiating the treatment. Quantification was performed by ELISA following standard procedures as previously described ( 26 ). Once collected, sera samples were stored frozen at −80°C until further processing.…”

“…Its immunomodulatory mechanism of action has been further studied in vitro and in vivo ( 23 , 24 ). MV130 is a mucosal TIbV used to prevent infections in patients with recurrent infections without known immunodeficiency, but also may have that role in immunocompromised patients ( 25 , 26 ). Mucosal TIbVs act directly on specific tissues where pathogens initiate or spread infections, decreasing the number of reinfections and also inducing tolerance ( 23 , 27 ).…”