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

Abstract

Infectious complications are a major cause of morbidity and mortality in B-cell hematological malignancies (HM). Prophylaxis for recurrent infections in HM patients with antibody deficiency consists of first-line antibiotics and when unsuccessful, gammaglobulin replacement therapy (IgRT). Recent knowledge of trained immunity-based vaccines (TIbV), such as the sublingual polybacterial formulation MV130, has shown a promising strategy in the management of patients with recurrent infections. We sought to determine the clinical benefit of MV130 in a cohort of HM patients with recurrent respiratory tract infections (RRTIs) who underwent immunization with MV130 for 3 months. Clinical information included the frequency of infections, antibiotic use, number of visits to the GP and hospitalizations previous and after MV130 immunotherapy. Improvement on infection rate was classified as: clear (>60% reduction of infection), partial (26%-60%) and low (≤25%) improvement. Fifteen HM patients (aged 42 to 80 years; nine females) were included in the study. All patients reduced their infection rate. Analysis of paired data revealed that the median (range, min - max) of respiratory infectious rate significantly decreased from 4.0 (8.0-3.0) to 2.0 (4.0-0.0) (p<0.001) at 12 months of MV130. A clear clinical improvement was observed in 53% (n = 8) of patients, partial improvement in 40% (n = 6) and low improvement in 7% (n = 1). These data correlated with a decrease on antibiotic consumption from 3.0 (8.0-1.0) to 1.0 (2.0-0.0) (p = 0.002) during 12 months after initiation of treatment with MV130. The number of infectious-related GP or emergency room visits declined from 4.0 (8.0-2.0) to 2.0 (3.0-0.0) (p<0.001), in parallel with a reduction in hospital admissions due to infections (p = 0.032). Regarding safety, no adverse events were observed. On the other hand, immunological assessment of serum IgA and IgG levels demonstrated an increase in specific antibodies to MV130-contained bacteria following MV130 immunotherapy. In conclusion, MV130 may add clinical benefit reducing the rate of infections and enhancing humoral immune responses in these vulnerable patients.

Keywords: IgA; MV130; hematological malignancies; prophylaxis; recurrent respiratory tract infections; trained immunity-based vaccines.

Conflict of interest statement

LC and CD-R belong to the Immunotek R+D Department. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Ochoa-Grullón, Benavente Cuesta, González Fernández, Cordero Torres, Pérez López, Peña Cortijo, Conejero Hall, Mateo Morales, Rodríguez de la Peña, Díez-Rivero, Rodríguez de Frías, Guevara-Hoyer, Fernández-Arquero and Sánchez-Ramón.

Figures

Figure 1

Flow chart of the study including enrolment, medical intervention, therapy and follow-up, and analysis. RRTIs, recurrent respiratory tract infection; IT, immunotherapy; GP, general practitioner; ER, emergency room.

Figure 2

Prophylaxis with MV130 reduces the incidence of respiratory infection rate (%) in patients with B cell hematological malignancies. (A, B) Number of respiratory tract infections one year before immunotherapy with MV130 (Pre) and in the 12 months after initiation of immunotherapy (Post) (A-tabulated, B-graph). (A, C) Percentage of improvement (reduction of infections) (A-tabulated, C-pie chart). Improvement was classified as: clear (>60% reduction of infectious episodes), partial (26-60% reduction of infectious episodes) and low (<25% reduction of infectious episodes). A total of 15 patients were included. Normal distribution was evaluated using Shapiro-Wilk test, and P value was calculated comparing infectious episodes pre and post immunotherapy with MV130 using Wilcoxon signed rank test.

Figure 3

MV130 cuts down on antibiotic and healthcare resource consumption. (A) Antibiotic consumption, (B) unscheduled medical visits, and (C) hospitalizations during the year before (Pre) and after (Post) the initiation of immunotherapy with MV130. Data from n=12 (A) n=15 (B, C) patients are displayed, Normal distribution was evaluated using Shapiro-Wilk test, and P values were calculated using Wilcoxon signed rank test. GP, general practitioner; ER, emergency room.

Figure 4

Prophylaxis with MV130 increases serum specific IgA antibody production. Serum IgA specific antibodies against (A) MV130 (bacterial mixture), (B) S. epidermidis, (C) S. aureus, (D) S. pneumoniae, (E) H. influenzae, (F) M. catarrhalis and (G) K. pneumoniae were quantified from patients before immunotherapy with MV130 (Pre), and 4 to 41 months after initiation of immunotherapy with MV130 (Post). Levels of antibodies were determined by ELISA. Sera samples from a total of 13 patients were included. Normal distribution was evaluated using Shapiro-Wilk test, and P values were calculated using Wilcoxon signed rank test.