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Observational Study
. 2021 Jun 4:12:675735.
doi: 10.3389/fimmu.2021.675735. eCollection 2021.

Sublingual Bacterial Vaccination Reduces Recurrent Infections in Patients With Autoimmune Diseases Under Immunosuppressant Treatment

Silvia Sánchez-Ramón  1 , Lidia Fernández-Paredes  1 , Paula Saz-Leal  2 , Carmen M Diez-Rivero  2 , Juliana Ochoa-Grullón  1 , Concepción Morado  3 , Pilar Macarrón  3 , Cristina Martínez  3 , Virginia Villaverde  4 , Antonia Rodríguez de la Peña  1 , Laura Conejero  2 , Keyla Hernández-Llano  1 , Gustavo Cordero  1 , Miguel Fernández-Arquero  1 , Benjamin Fernández- Gutierrez  3 , Gloria Candelas  3
Affiliations
Observational Study

Sublingual Bacterial Vaccination Reduces Recurrent Infections in Patients With Autoimmune Diseases Under Immunosuppressant Treatment

Silvia Sánchez-Ramón et al. Front Immunol. .

Abstract

Introduction: Conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use.

Objective: To evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs.

Methods: An observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year.

Results: Forty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p<0.001), lower respiratory tract infections (LRTI) (p=0.009) and upper respiratory tract infections (URTI) (p=0.006) at 12-mo with respect to the previous year was observed. Antibiotic prescriptions and unscheduled medical visits decreased significantly (p<0.020) in all groups. Hospitalization rate also declined in patients with RRTI (p=0.019). The clinical benefit demonstrated was concomitant to a significant increase in both anti-S. pneumoniae IgA and IgG antibodies following MV130 vaccination.

Conclusions: Sublingual polybacterial vaccines prevent recurrent infections in patients with SAD under treatment with immunosuppressant therapies, supporting a broad non-specific anti-infectious effect in these patients.

Keywords: MV130; MV140; biological therapies; mucosal bacterial vaccines; recurrent infections; systemic autoimmune disease.

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Conflict of interest statement

PS-L, CD-R and LC are employees of Inmunotek S.L. SS-R has received in the past a fee as speaker from Inmunotek S.L. 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.

Figures

Figure 1
Figure 1
Flow-chart of the study. RRTI, recurrent respiratory tract infections; RUTI, recurrent urinary tract infections; IT, immunotherapy.
Figure 2
Figure 2
MV140 and MV130 induce a significant fall-off in the incidence of recurrent respiratory and urinary infections. (A-C) Number of infectious episodes scored 1 year prior to vaccination and throughout 12 months after the initiation of immunotherapy (MV130 or MV140) in subjects suffering RRTI (A), RUTI (B) or both (C). RRTI: Recurrent respiratory tract infections, either upper (URTI), lower (LRTI) or both (total RTI); RUTI: Recurrent urinary tract infections. Data from 14 (A), 19 (B) or 8 (C) subjects are shown. Lines link paired values. Normal distribution was evaluated using the Shapiro-Wilk test. P values were calculated using Wilcoxon signed-rank test.
Figure 3
Figure 3
Prophylaxis with MV130 and MV140 reduce the consumption of healthcare resources. (A–C) Antibiotic consumption (A), unscheduled medical visits (emergency unit and specialist) (B) and hospitalization (C) in subjects suffering RRTI (left panel), RUTI (middle panel) or both (right panel), during the year prior (pre) and after (post) the initiation of the treatment (MV130 or MV140). RRTI: Recurrent respiratory tract infections; RUTI: Recurrent urinary tract infections. Bars show the relative abundance of the number of antibiotic courses (A), unscheduled medical visits (B) or hospital admissions (C) in the total of subjects recorded. Data from 29 (A), 33 (B) or 34 (C) subjects, receiving either MV130 or MV140 according to their pathology are shown. Normal distribution was evaluated using the Shapiro-Wilk test. P values were calculated using Wilcoxon signed-rank test, ns, non-significant.
Figure 4
Figure 4
Prophylaxis with mucosal bacterial vaccines increases serum antibody production. (A–D) Serum IgA (left panels) and IgG (right panels) antibodies against the specified pathogens (A, C) or the bacterial mixture (B, D), collected from subjects before vaccination and at 18-45 months after initiating either MV130 or MV140 immunotherapy. Data in each individual subject are normalized to the corresponding pre-vaccination value. Results from N=6 (MV130) or N=5 (MV140) individuals are shown as mean+SEM for each immunoglobulin. P values were calculated using one sample t-test with 1 as theoretical mean value.
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