Bacterial Lysates as Immunotherapies for Respiratory Infections: Methods of Preparation

Abstract

Bacterial lysates, prepared from the microorganisms most frequently involved in human Respiratory Tract Infections (RTIs) have been in the market for several decades, and at present, several different brands are available in many countries worldwide. They all claimed to exert local and systemic immunomodulatory effects but different clinical trials show disparate results between them. The lack of consistency of predicted therapeutic effects has undermined their clinical use and hampered licensing in several countries. One explanation for such lack of consistency in the results is that their methods of preparation are also very different. Here, we review the available literature describing methods of preparation of bacterial lysates, including patent disclosure documents. We found a great variety of methodologies of preparation and a lack of standardized procedures among them. The main conclusion of our study is that there is a clear need for standardized protocols of production to obtain comparable results in clinical trials worldwide.

Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation

“…It has been argued that the means by which the lysates are prepared (mechanical vs chemical disruption of bacterial cells) has direct influence in the immunostimulant activity of the product ( 5 ). Thus, we prepared two different PBL with the same bacterial composition but using either mechanical (PMBL) or alkaline treatment (PABL) as method of bacterial disruption, for side-by-side comparison.…”

“…Improved methods for characterization of bacterial lysate components would result in more reliable and comparable products. Most descriptions of commercial lysates, either in the literature or in patent filling just quantifies proteins and carbohydrates ( 5 , 34 – 36 ). We have recently proposed that the use of MALDI-TOF technique for characterization and identification of biomarkers of biological activity that helps to evaluate the consistency and reproducibility of batch production would represent an advance in this sense ( 29 ).…”

“…These strains are grown independently, harvested and then lysed and mixed to obtain the PBLs used in the clinics. The cell lysis is a key stage for obtaining bacterial lysates that works effectively and different methods have been studied, being the most used alkaline and mechanical lysis (5)(6)(7)(8). PBL can be administered orally, nasally or sublingually, and are capable of activating mucosal-associated lymphoid tissues, both locally and distally (7,9).…”

Using of topical bacterial lysates in modern clinical practice

“…Это лекарственное средство представляет собой сбалансированный комплекс лизатов, а именно Lactobacillus johnsonii, Lactobacillus helveticus, Lactobacillus delbrueckii ss lactis, Lactobacillus fermentum, Streptococcus pyogenes groupe A, Enterococcus faecium, Enterococcus faecalis, Staphylococcus gordinii, Staphylococcus aureus, Klebsiella pneumoniae ss pneumoniae, Corynebacterium pseudodiphtheriticum, Fusobacterium nucleatum ss fusiforme и Candida albicans, имеющих в своем составе компоненты, активизирующие противовоспалительные механизмы [34][35][36]. Противовоспалительная активность препарата Имудон ® выражается в снижении общего числа лейкоцитов и гранулоцитов в крови, уровня циркулирующего TNF-α и гистологических признаков местной воспалительной реакции [37]. Имудон ® в момент рассасывания взаимодействует со слизистой оболочкой непосредственно в очаге инфекции, где и активирует иммунный ответ для борьбы с первопричиной заболевания.…”

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“…Improved methods for characterization of bacterial lysate components would result in more reliable and comparable products. Most descriptions of commercial lysates, either in the literature or in patent filling just quantifies proteins and carbohydrates (5,(34)(35)(36). We have recently proposed that the use of MALDI-TOF technique for characterization and identification of biomarkers of biological activity that helps to evaluate the consistency and reproducibility of batch production would represent an advance in this sense (29).…”