A Review Article on Immunological Effects of Bacterial Lysate in Upper Respiratory Tract Infection

Abstract

Bacterial lysates are immunostimulants clinically used to prevent respiratory tract infections (RTIs). They enhance both innate and adaptive immune responses, demonstrating efficacy in restoring epithelial barrier integrity, activating ILC3 and dendritic cells, and promoting a Th1 response. Additionally, they stimulate the production of specific serum IgG and salivary IgA, providing cross-protection against other pathogens via trained immunity. Clinical studies report a reduction in RTI frequency and severity in patients pretreated with bacterial lysates, alongside a potential protective effect against disease progression in conditions like COPD, without significant side effects. Bacterial lysates (BLs), composed of bacterial antigens, have been utilized for decades to reduce the risk of recurrent respiratory tract infections in both pediatric and adult populations. Recent research has explored their application in allergology, particularly for allergic rhinitis (AR). The findings indicate that incorporating BLs into standard therapy for seasonal or perennial AR alleviates nasal symptoms and reduces the need for antiallergic medications in both children and adults. Furthermore, BLs demonstrate a favorable safety profile. The analysis reveals that therapeutic effects emerge within 2–6 weeks of treatment initiation and persist for at least three months post-treatment.

Keywords

Introduction

Drug	Bacterial Lysate Preparation Method	Bacterial Content	Formulation	Dosage/dose
Ismigen	Polyvalent, mechanical	48 MLD	Sublingual tablets	7 mg for children 3 years of age, once daily for 10 consecutive days each month for 3 months
BronchoVaxom	Polyvalent, chemical	3.5 mg; 7 mg	Capsules	3.5 mg for 6-12 months, 7 mg for 12 years of age, according to Patient Information Leaflet
Luivac	Polyvalent, chemical	1mld	Tablets	3 mg for 2 years of age, according to Patient Information Leaflet
Ribomunyl	Kleinsiella pneumoniae membrane fraction proteoglycan	Ribosomes/ribosomal RNA: k. pneumoniae 35p/w str. Pneumoniae 3p/w str. Pyogenes 3p/w H. influenzae,0.5p/w	Tablets, granules	Tab:0.525mg, granules:0.750mg>2 yrs of age, according to patients information leaflet

Figure No.1: The Immune Mechanisms Affected by Bacterial Lysates

Bacterial Species and Lysis Methods:

Key pathogens involved in respiratory tract infections include Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae, Klebsiella ozaenae, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus viridans, and Moraxella catarrhalis. However, the use of alkaline lysis in bacterial lysate preparation may lead to protein denaturation, reducing the immunogenicity of bacterial antigens and consequently diminishing the immune response.  Polyvalent Mechanical Bacterial Lysate (PMBL) is a lysate derived from a broad spectrum of pathogenic bacteria, including the most common upper and lower respiratory tract pathogens (S. aureus, S. viridans, S. pyogenes, K. pneumoniae, K. ozaenae, H. influenzae serotype B, M. catarrhalis, and S. pneumoniae), produced through mechanical lysis [13]. This method is highly effective, achieving lysis in 80–100% of the bacterial cells, while preserving antigenic integrity and enhancing immunogenicity.

Principle of Bacterial Lysates' Activity:

The enhanced elimination of bacterial pathogens in recurrent respiratory infections is attributed to the activation of the immune system's memory. Bacterial lysates interact with mucosa associated lymphoid tissue (MALT), which is continuously exposed to pathogenic antigens. MALT comprises gut-associated lymphoid tissue (GALT), bronchus-associated lymphoid tissue (BALT), nasal-associated lymphoid tissue (NALT), and lymphoid tissues of lacrimal, salivary, mammary, and urogenital glands. Its primary function is the production of secretory IgA (sIgA) antibodies, which protect by coating microbial cells, preventing their adhesion, neutralizing toxins, and exerting bacteriostatic effects.  Memory B cells continuously secrete low levels of antibodies, enabling a rapid and robust response upon re-exposure to the same pathogens. Secondary immune responses are more rapid, efficient, and robust than primary responses, requiring lower antigen levels to trigger and producing higher antibody quantities with slower decline rates. The affinity of antibodies in secondary responses is also higher. This enhanced immune readiness can persist for extended periods, but to sustain effectiveness, immunomodulatory agents must be administered periodically.

Safety Profile of Bacterial Lysates:

A systematic review found no statistically significant differences in adverse event incidence between bacterial lysate- and placebo-treated groups. The most commonly reported side effects included rash, vomiting, nausea, abdominal pain, and diarrhea. No serious or life-threatening adverse events were observed, and no association was found between bacterial lysate use and autoimmune diseases. Occasional mild side effects, similar to those seen with vaccines, are attributed to immune system activation, particularly in cases of severe immunosuppression where inactivated pathogens may trigger inflammation.

Limitations of Bacterial Lysate Treatment:

Bacterial lysate therapy has certain limitations, particularly concerning patient age, requiring caution in individuals with immature immune systems. Immunostimulatory treatment should be administered at appropriate intervals to allow for immune system regeneration, as laboratory analyses indicate an initial depletion of peripheral immunocompetent cell reserves during immune-stimulation.

Recommendations for the Use of Bacterial Lysates:

The initiation of immunotherapy with bacterial lysates should be preceded by an evaluation of the immune system's quantitative and functional status, with treatment monitored through clinical assessments and immunodiagnostic tests. Despites favorable outcomes from clinical trials, bacterial lysates are not recommended for use in acute infectious diseases, immunodeficiency’s, autoimmune or rheumatic conditions, active tuberculosis, or cardiopulmonary insufficiency.

CONCLUSION:

Oral immunomodulatory agents available on the Polish market have proven effective in preventing and managing both acute and recurrent upper respiratory tract infections (URTIs) in pediatric and adult populations. Bacterial lysates vary in chemical composition, preparation methods, dosage, administration routes, and age indications for pediatric use. These agents are generally well-tolerated, with only mild adverse effects reported, and their high efficacy, as demonstrated in clinical trials, supports their use across all age groups, particularly during periods of heightened URTI prevalence. Bacterial lysates enhance immune-protection, reduce the frequency and recurrence of respiratory infections in both children and adults, alleviate respiratory symptoms, shorten the duration of infection-related fever, and decrease the need for antibiotic therapy.

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