The effect of passages during Japanese BCG vaccine production on genetic stability and protective efficacy

Seki, Masaaki; Udagawa, Tadashi; Sugawara, Isamu; Iwama, Kenji; Honda, Ikuro; Fujita, Isao; Hashimoto, Akira; Yano, Ikuya; Yamamoto, Saburo

doi:10.1016/j.vaccine.2011.12.101

Cited by 6 publications

(6 citation statements)

References 10 publications

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“…Moreover, the CSBL showed the highest number of variants compared to the reference strain and the number of passages on Sauton broth was more than the other two media (34 passages); therefore, the increased variants may be ralated to the increased passages. In contrary to the present study, Seki et al investigated the effect of passages during BCG Tokyo 172 production on genetic stability using several specific genomic regions [42]. This study reported no differences between seed lot, 8th and 20th passages of the vaccine product, indicating genetic stability in the tested regions.…”

Section: Plos Onecontrasting

confidence: 85%

“…In contrary to the present study, Seki et al . investigated the effect of passages during BCG Tokyo 172 production on genetic stability using several specific genomic regions [ 42 ]. This study reported no differences between seed lot, 8th and 20th passages of the vaccine product, indicating genetic stability in the tested regions.…”

Section: Discussionmentioning

confidence: 99%

“…This study reported no differences between seed lot, 8th and 20th passages of the vaccine product, indicating genetic stability in the tested regions. This study also revealed that the Multiplex PCR is not sufficient to detect the low number of variants, SNPs and short InDels in the vaccine [42], and in this study we decided to use the whole genome sequencing method. In addition, Trovero et al examined the genetic stability of BCG Pasteur 1173P2 after serial passages by examining only some specific genomic regions [43].…”

Section: Plos Onementioning

confidence: 99%

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The effect of in vitro consecutive passages and culture medium on the genetic variations in BCG Pasteur 1173P2 vaccine

et al. 2023

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Since the introduction of the Bacillus Calmette–Guérin (BCG) vaccine, the genomes of vaccine strains have undergone variations due to repeated passages in different laboratories and vaccine production facilities. Genetic variations have been considered as one of the effective factors in the BCG variable protective efficacy. Consecutive subcultures have been shown to play an essential role in causing genetic variations in several microorganisms, including Mycobacterium bovis BCG. Therefore, the world health organization (WHO) recommendation to limit the passages of master seed lot in the BCG vaccine production should be considered. Besides, the role of other external variables such as quality of the raw ingredients of the culture media, the type of the culture medium and the cultivation methods in the vaccine production has been poorly studied. Here, the effect of passages and culture medium on genetic variations in a BCG seed lot was investigated during a year. The findings of this study revealed a total of 19 variants compared to seed lot while the passages were more than the number recommended by WHO. The first culture of seed lot in the Sauton broth and Middlebrook 7H9 media, and the last subculture in Sauton broth had the least and the most variants, respectively. The observation of the higher number of variants in the last cultures on Sauton broth and Middlebrook 7H9 in comparison to the first and the middle cultures may indicate the effect of passages on the genetic variations in BCG. Additionally, more variants in BCG grown in the Sauton broth do not necessarily represent the greater ability of this medium to cause genetic mutations. For a better conclusion, it is required to examine the medium components as independent variables.

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Section: Plos Onecontrasting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

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The effect of in vitro consecutive passages and culture medium on the genetic variations in BCG Pasteur 1173P2 vaccine

et al. 2023

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“…During the next decades, maintenance of the BCG strain progenies by further passages using different culture media and transfer schedules in different countries contributed to the in vitro evolution of BCG. The production of seed stocks without lyophilization until the 1960s resulted in the generation of BCG daughter strains (substrains) with variable morphological, culture, antigenic characteristics, and residual virulence due to adaptation in vitro [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

et al. 2020

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Background: The only licensed live Bacille Calmette-Guérin (BCG) vaccine used to prevent severe childhood tuberculosis comprises genetically divergent strains with variable protective efficacy and rates of BCG-induced adverse events. The whole-genome sequencing (WGS) allowed evaluating the genome stability of BCG strains and the impact of spontaneous heterogeneity in seed and commercial lots on the efficacy of BCG-vaccines in different countries. Our study aimed to assess sequence variations and their putative effects on genes and protein functions in the BCG-1 (Russia) seed lots compared to their progeny isolates available from immunocompetent children with BCG-induced disease (mainly, osteitis). Results: Based on the WGS data, we analyzed the links between seed lots 361, 367, and 368 used for vaccine manufacture in Russia in different periods, and their nine progeny isolates recovered from immunocompetent children with BCG-induced disease. The complete catalog of variants in genes relative to the reference genome (GenBank: CP013741) included 4 synonymous and 8 nonsynonymous single nucleotide polymorphisms, and 3 frameshift deletions. Seed lot 361 shared variants with 2 of 6 descendant isolates that had higher proportions of such polymorphisms in several genes, including ppsC, eccD5, and eccA5 involved in metabolism and cell wall processes and reportedly associated with virulence in mycobacteria. One isolate preserved variants of its parent seed lot 361 without gain of further changes in the sequence profile within 14 years.

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“…Genetic stability is a critical indicator of vaccine quality ( 23 , 24 ). To ensure the genetic stability of the BCG vaccine, it is stipulated that no more than 12 generations of seed strains be used in its production ( 25 ). Hence, to ensure vaccine quality, it is necessary to study and monitor the vaccine’s stability.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the efficacy of Aeromonas veronii ΔhisJ vaccine in Carassius auratus via different immunization routes

Wu,

Ma,

Pan

et al. 2024

Front. Vet. Sci.

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IntrodctionAeromonas veronii is a significant pathogen to various aquatic life. Infections in fish can lead to high mortality rates, causing substantial economic losses in aquaculture. Vaccination is proposed as a substitute for antibiotics in aquaculture to decrease disease-related mortality and morbidity. Our study previously constructed a hisJ-deleted strain of A. veronii, which provided protective effect to Loach.MethodsTo further assess the vaccine’s applicability, this study evaluated its genetic stability and safety, and the immune protective effects in Carassius auratus through four distinct administration routes: intraperitoneal injection, intramuscular injection, oral administration, and immersion, to determine the efficacy of these administration routes.ResultsThe results showed that the vaccine remained genetically stable after 45 generations. Immunization via these administration routes was safe for Carassius auratus, with intraperitoneal and intramuscular injections causing stronger adverse reactions. Immersion immunization resulted in mild adverse reactions, and no significant adverse reactions were observed following oral immunization. Immunizing Carassius auratus at safe concentrations via these routes enhanced the phagocytic activity in serum, increased the levels of non-specific immune-related enzymes (ACP, AKP, C3, C4, LZM, SOD, and IgM), and improved specific serum antibody levels. It also elevated levels of cytokines related to inflammatory responses (IL-1β, IL-10, TNF-α, TGF-β) in organ tissues (liver, spleen, kidney, mid-post intestine, and gills). The survival rates of Carassius auratus were measured after challenging with the virulent strain A. veronii TH0426, resulting in the relative survival rates of 64% for Intraperitoneal vaccine group, 56% for Intramuscular vaccine group, 52% for oral vaccine group, and 48% for immersion vaccine group. Analysis of bacterial load in the liver, spleen, and kidney post-challenge showed a decreasing trend in the control group, indicating that the vaccine strain ΔhisJ could gradually restrict the rapid proliferation of bacteria in these tissues, thereby providing a certain level of immune protection against A. veronii.DiscussionIn brief, the vaccine strain ΔhisJ can serve as a safe live attenuated vaccine for Carassius auratus, and this study lays the foundation for the development of live attenuated vaccines against Aeromonas veronii.

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The effect of passages during Japanese BCG vaccine production on genetic stability and protective efficacy

Cited by 6 publications

References 10 publications

The effect of in vitro consecutive passages and culture medium on the genetic variations in BCG Pasteur 1173P2 vaccine

The effect of in vitro consecutive passages and culture medium on the genetic variations in BCG Pasteur 1173P2 vaccine

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

Comparison of the efficacy of Aeromonas veronii ΔhisJ vaccine in Carassius auratus via different immunization routes

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