Developing a Live Probiotic Vaccine Based on the Enterococcus faecium L3 Strain Expressing Influenza Neuraminidase

Desheva, Yulia; Leontieva, Galina; Kramskaya, Tatiana; Gupalova, Tatiana; Losev, Igor; Kuleshevich, Eugenia; Bormotova, Elena; Kopteva, Olga; Kudar, Polina; Suvorov, Alexander

doi:10.3390/microorganisms9122446

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…It's important to note that we have previously demonstrated the efficacy of probiotic oral vaccines against viral and bacterial respiratory infections too [1,53]. This suggests a potential similar outcome for coronavirus infection, but empirical validation is necessary.…”

Section: Discussionmentioning

confidence: 78%

SARS-CoV-2 Spike Protein-Expressing Enterococcus for Oral Vaccination: Immunogenicity and Protection

Suvorov,

Loginova,

Leontieva

et al. 2023

Preprint

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The COVID-19 pandemic was declared in March 2020 and is still ongoing. The course of the epidemic remains uncertain, and mutations in the coronavirus, as well as the emergence of new variants of concern, make it possible that there will be periodic surges in the number of cases. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the development of pan-coronavirus vaccines that stimulate the production of antibodies against conserved elements of the virus. Another approach could be the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. With a well-established safety profile and the ability to transform into vaccine candidates, probiotic bacteria have significant research potential. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters.

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Section: Discussionmentioning

confidence: 78%

SARS-CoV-2 Spike Protein-Expressing Enterococcus for Oral Vaccination: Immunogenicity and Protection

Suvorov,

Loginova,

Leontieva

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This inserted fragment is transcribed, leading to the synthesis of the coronavirus protein on corresponding messenger RNAs, detectable on the surface of L3-SARS [ 25 ]. It is noteworthy that we have previously successfully employed this genetic engineering technique to obtain vaccine variants targeting GBS, pneumococci [ 22 , 23 ], and, more recently, influenza A virus [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…We are currently investigating the protective efficacy of the constructed vaccine strain L3-SARS. Similar live recombinant influenza vaccines modified with the NA and HA inserts of the influenza virus have already demonstrated a protective effect [ 37 , 38 ]. In conclusion, our results suggest that the Enterococcus faecium L3 strain containing epitopes of SARS-CoV-2 S protein can stimulate a specific immune response against SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Immune Response to Mucosal Immunization with an Oral Probiotic-Based Vaccine in Mice: Potential for Prime-Boost Immunization against SARS-CoV-2

Leontieva,

Gupalova,

Desheva

et al. 2023

IJMS

Self Cite

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Following the conclusion of the COVID-19 pandemic, the persistent genetic variability in the virus and its ongoing circulation within the global population necessitate the enhancement of existing preventive vaccines and the development of novel ones. A while back, we engineered an orally administered probiotic-based vaccine, L3-SARS, by integrating a gene fragment that encodes the spike protein S of the SARS-CoV-2 virus into the genome of the probiotic strain E. faecium L3, inducing the expression of viral antigen on the surface of bacteria. Previous studies demonstrated the efficacy of this vaccine candidate in providing protection against the virus in Syrian hamsters. In this present study, utilizing laboratory mice, we assess the immune response subsequent to immunization via the gastrointestinal mucosa and discuss its potential as an initial phase in a two-stage vaccination strategy. Our findings indicate that the oral administration of L3-SARS elicits an adaptive immune response in mice. Pre-immunization with L3-SARS enhances and prolongs the humoral immune response following a single subcutaneous immunization with a recombinant S-protein analogous to the S-insert of the coronavirus in Enterococcus faecium L3.

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“…When tested in mice, the created prototypes of oral vaccines induced antibodies either directed at the NA protein or M2e-specific antibodies. It was the L3-LAH+M2e vaccine that provided 100% survival in experimen-tal animals, which is promising for further development and testing a candidate vaccine for influenza prevention [123]. The possibility of creating a vaccine against the H1N1 influenza virus by integrating the neuraminidase (NA) genes into Ec.…”

Section: Antiviral Vaccines Based On Recombinant Probioticsmentioning

confidence: 99%

Recombinant Probiotic Preparations: Current State, Development and Application Prospects

Khablenko

Danylenko

Yalovenko

et al. 2023

Innov Biosyst Bioeng

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The article is devoted to the latest achievements in the field of research, development, and implementation of various types of medicinal products based on recombinant probiotics. The benefits of probiotics, their modern use in medicine along with the most frequently used genera and species of probiotic microorganisms were highlighted. The medicinal and therapeutic activities of the studied probiotics were indicated. The review suggests various methods of creating recombinant probiotic microorganisms, including standard genetic engineering methods, as well as systems biology approaches and new methods of using the CRISPR-Cas system. The range of potential therapeutic applications of drugs based on recombinant probiotics was proposed. Special attention was paid to modern research on the creation of new, more effective recombinant probiotics that can be used for various therapeutic purposes. Considering the vast diversity of therapeutic applications of recombinant probiotics and ambiguous functions, their use for the potential treatment of various common human diseases (non-infectious and infectious diseases of the gastrointestinal tract, metabolic disorders, and allergic conditions) was investigated. The prospects for creating different types of vaccines based on recombinant probiotics together with the prospects for their implementation into medicine were considered. The possibilities of using recombinant probiotics in veterinary medicine, particularly for the prevention of domestic animal diseases, were reviewed. The prospects for the implementation of recombinant probiotics as vaccines and diagnostic tools for testing certain diseases as well as modeling the work of the human digestive system were highlighted. The risks of creation, application, including the issues related to the regulatory sphere regarding the use of new recombinant microorganisms, which can potentially enter the environment and cause unforeseen circumstances, were outlined.

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Developing a Live Probiotic Vaccine Based on the Enterococcus faecium L3 Strain Expressing Influenza Neuraminidase

Cited by 9 publications

References 43 publications

SARS-CoV-2 Spike Protein-Expressing Enterococcus for Oral Vaccination: Immunogenicity and Protection

SARS-CoV-2 Spike Protein-Expressing Enterococcus for Oral Vaccination: Immunogenicity and Protection

Evaluation of Immune Response to Mucosal Immunization with an Oral Probiotic-Based Vaccine in Mice: Potential for Prime-Boost Immunization against SARS-CoV-2

Recombinant Probiotic Preparations: Current State, Development and Application Prospects

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