Composition for enhancing vaccine immune response, comprising intestinal microorganisms as active ingredients

Abstract

The present invention relates to an intestinal microorganism-based composition for enhancing the efficacy of vaccinations, in particular, the persistence of antibody reactions and booster effects. The present inventors have found that specific intestinal microorganisms are significantly abundant in individuals having a long antibody half-life following vaccination with an mRNA vaccine or an adenovirus vector vaccine, or exhibiting a high immune response upon booster vaccination. Specifically, it was found that a specific microbial community including Faecalibacterium prausnitzii is associated with antibody persistence and booster response enhancement following mRNA vaccination, and Escherichia coli is associated with antibody persistence following adenovirus vector vaccination.

Description

Composition for enhancing vaccine immune response containing intestinal microorganisms as active ingredients

[0001] The present invention relates to a health functional food or vaccine adjuvant composition and its use, which includes a specific intestinal microorganism as an active ingredient to enhance the efficacy of vaccination, and in particular, to extend the duration of antibodies produced after vaccination and to strengthen the immune response at the time of booster vaccination.

[0002] The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis. In response, novel vaccine platforms, including adenovirus vector vaccines, protein subunit vaccines, and mRNA vaccines, have been rapidly developed and played a crucial role in controlling the global pandemic.

[0003] These vaccines typically elicit a robust initial immune response, with peak antibody titers occurring approximately three to four weeks after the second dose. However, these antibodies have been observed to gradually decline over time, returning to levels similar to the initial immune response after approximately six months. Antibody persistence after vaccination is crucial for maintaining long-term protection in individuals and establishing herd immunity. Antibody persistence is primarily maintained by long-lived plasma cells located in the bone marrow, while memory B cells enable rapid and effective immune responses upon re-exposure to the relevant virus.

[0004] The strength and durability of immune responses following vaccination vary significantly across individuals, influenced by various host factors. Among these, the gut microbiota is known to play a crucial role. Gut microbes play a central role in the training and maturation of key components of the host immune system, particularly the adaptive immune system. Gut microbes stimulate and shape the adaptive immune system through exposure to bacterial components and active metabolites, and this interaction is essential for maintaining intestinal homeostasis and suppressing inflammation.

[0005] Several recent studies have reported an association between peak antibody titers and gut microbiota after SARS-CoV-2 vaccination. For example, a study by Ng et al. reported that Bifidobacterium adolescentis showed a positive correlation with neutralizing antibodies in subjects with high neutralizing antibodies to the CoronaVac vaccine, and Roseburia faecis showed a positive correlation with neutralizing antibodies in BNT162b2 vaccine recipients (Ng SC, Peng Y, Zhang L, et alGut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse eventsGut 2022;71:1106-1116.). In addition, a study by Lynn et al. reported that Streptococcus bovis showed a positive correlation, and Bacteroides and Prevotella showed a negative correlation with vaccine response (Lynn, DJ, Benson, SC, Lynn, MA et al. Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms. Nat Rev Immunol 22, 33-46 (2022)).

[0006] However, these prior art studies primarily focus on the initial immunogenicity after vaccination, i.e., the peak antibody response. According to the prior art review report, existing studies do not address the specific correlation between the gut microbiota and the "persistence" or "durability" of vaccine-induced antibodies, i.e., extending antibody half-life or enhancing immune responses during booster vaccination.

[0007] Therefore, to address the significant technical challenge of waning immunity over time after vaccination, new means are urgently needed to extend antibody persistence and maximize the effectiveness of booster vaccination.

[0008] The technical problem to be achieved by the present invention is to provide a health functional food composition for enhancing antibody persistence after SARS-CoV-2 mRNA vaccination, which comprises, as an active ingredient, one or more microorganisms selected from the group consisting of Faecalibacterium prausnitzii, Prevotella microorganisms, Gemmiger formicilis, and Bacteroides dorei.

[0009] However, the technical problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

[0010] In order to solve the above problem, the present invention provides a health functional food composition for enhancing antibody persistence after SARS-CoV-2 mRNA vaccination, comprising as an active ingredient at least one selected from the group consisting of Faecalibacterium prausnitzii, Prevotella genus microorganisms, Gemmiger formicilis, and Bacteroides dorei.

[0011] According to one side, the above Prevotella genus microorganism may be Prevotella_uc or PAC001304_s.

[0012] According to one aspect, the composition may be formulated into capsules, powders, tablets or liquids.

[0013] According to another embodiment of the present invention, a health functional food composition for enhancing antibody persistence after vaccination with a SARS-CoV-2 adenovirus vector vaccine, comprising Escherichia coli as an active ingredient, is provided.

[0014] According to one aspect, the composition may be formulated in the form of capsules, powder, tablets or liquid.

[0015] According to another embodiment of the present invention, an adjuvant composition for enhancing an immune response upon SARS-CoV-2 vaccine booster vaccination is provided, comprising as an active ingredient at least one microorganism selected from the group consisting of Faecalibacterium prausnitzii, Peptoniphilus duerdenii, Mogibacterium genus JR_s, Ruminococcaceae genus PAC001048_s, and Anaerococcus provencensis.

[0016] According to one side, the SARS-CoV-2 vaccine may be an mRNA vaccine.

[0017] According to another embodiment of the present invention, there is provided a method comprising the steps of: preparing biological samples separated from a plurality of subjects of at least two different groups;

[0018] A step of analyzing a microbial community from the above sample using LEfSe (linear discriminant analysis (LDA) Effect Size);

[0019] A step of predicting that, as a result of LEfSe analysis, if the LDA score of any one or more microorganisms among Faecalibacterium prausnitzii, Prevotella genus microorganisms, Gemmiger formicilis, and Bacteroides dorei in a specific group is 2.0 or higher, the subject belonging to that group will have better antibody durability after SARS-CoV-2 mRNA vaccination than the subject belonging to another group;

[0020] A method for providing personalized vaccination information to a subject, including:

[0021] According to one side, the good antibody durability may mean that the antibody half-life between 3 weeks and 6 months after the second vaccination is longer than the median of the cohort.

[0022] The composition of the present invention can extend the half-life of antibodies produced after vaccination, providing a more sustained preventive effect. This reduces the need for frequent booster vaccinations and contributes to maintaining long-term herd immunity.

[0023] In addition, the vaccine adjuvant composition of the present invention can enhance the immune response when a booster vaccine is administered, thereby maximizing the overall vaccine efficacy, including the ability to respond to mutant viruses.

[0024] The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the detailed description of the present invention or the composition of the invention described in the claims.

[0025] Figure 1 is a schematic diagram illustrating the overall study design of the present invention. A total of 176 fecal samples were collected, but 13 samples of poor quality were excluded from analysis. Ultimately, 36 samples were collected after the first vaccination (V1), 39 samples after the second vaccination (V2), and 44 samples at the third and fourth follow-up observations (V3, V4). Blood samples were collected along with fecal samples at each time point and used to assess anti-Spike (anti-S) antibody responses.

[0026] Figure 2 compares the alpha and beta diversity of the gut microbiome between groups with slow and rapid declines in anti-S antibody titers in the BNT162b2 vaccination cohort. (A) shows the alpha diversity index (ACE, Simpson), and (B) visualizes beta diversity using principal coordinate analysis (PCoA) using the Jensen-Shannon algorithm.

[0027] Figure 3 shows the results of a shotgun sequencing-based analysis of the compositional differences in the gut microbiome between high- and low-response groups after BNT162b2 booster vaccination. (A) shows the differences in microbial composition at the species level, and (B) shows the differences at the genus level.

[0028] To address the aforementioned challenges, the present inventors have, for the first time, identified a significant correlation between specific intestinal microorganisms and antibody half-life and booster responses following SARS-CoV-2 vaccination, thereby completing a composition capable of enhancing vaccine efficacy.

[0029] The present invention provides a health functional food composition for enhancing antibody persistence after SARS-CoV-2 mRNA vaccination, comprising as an active ingredient at least one selected from the group consisting of Faecalibacterium prausnitzii, Prevotella genus microorganisms, Gemmiger formicilis, and Bacteroides dorei.

[0030] The above Faecalibacterium prausnitzii may preferably have a 16s rRNA sequence represented by SEQ ID NO: 1. The above Prevotella genus microorganism may preferably be Prevotella_uc having a 16s rRNA sequence represented by SEQ ID NO: 2 or PAC001304_s having a 16s rRNA sequence represented by SEQ ID NO: 3. The above Gemmiger formicilis may preferably have a 16s rRNA sequence represented by SEQ ID NO: 4, and the above Bacteroides dorei may preferably have a 16s rRNA sequence represented by SEQ ID NO: 5.

[0031] The term "antibody persistence enhancement" as used herein means slowing the rate at which the blood concentration of antibodies produced after vaccination decreases, i.e., extending the biological half-life of antibodies.

[0032] The term “subject” as used herein means any mammal, including humans, that requires vaccination with a SARS-CoV-2 vaccine.

[0033] The term "active ingredient" used in this specification means an ingredient that exhibits the desired effect in itself, i.e., the effect of enhancing a vaccine immune response, and in the present invention, it is a concept that includes a specific intestinal microorganism itself or its culture, concentrate, dried substance, dead cells, lysate, etc.

[0034] The term "composition" as used herein refers to a mixture that may additionally include excipients, diluents, carriers, etc. commonly used in formulations in addition to the active ingredient. The composition of the present invention may be provided in the form of a "health functional food," a "pharmaceutical composition," or a "vaccine adjuvant composition."

[0035] The above SARS-CoV-2 mRNA vaccine may preferably be BNT162b2.

[0036] The health functional food of the present invention can be used in a variety of applications, including pharmaceuticals, foods, and beverages for improving the intestinal environment. Examples of the functional food of the present invention include various foods, candies, chocolates, beverages, gum, tea, vitamin complexes, and health supplements, and can be used in the form of powders, granules, tablets, capsules, or beverages.

[0037] The health functional food of the present invention may be added to food or beverages for the purpose of improving the intestinal environment. At this time, the amount of the extract in the food or beverage may generally be 0.01 to 50 wt%, preferably 0.1 to 20 wt%, of the total food weight for the health functional food composition of the present invention, and may be added at a rate of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml for the health beverage composition.

[0038] The health beverage composition of the present invention has no particular restrictions on the liquid component other than containing the strain as an essential component in the indicated ratio, and may contain various flavoring agents or natural carbohydrates as additional ingredients like a typical beverage. Examples of the above-described natural carbohydrates include common sugars such as monosaccharides such as glucose or fructose, disaccharides such as maltose, sucrose, and lactose, polysaccharides such as oligosaccharides, dextrin, and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, flavoring agents (stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic sweeteners (saccharin, aspartame, etc.) can be advantageously used. The ratio of the above-described natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g, per 100 ml of the composition of the present invention.

[0039] In addition to the above, the composition of the present invention may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juice and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of these additives is not so critical, but is typically selected in the range of 0 to about 50 parts by weight per 100 parts by weight of the composition of the present invention.

[0040] According to one side, the above Prevotella genus microorganism may be Prevotella_uc or PAC001304_s.

[0041] According to another embodiment of the present invention, a health functional food composition for enhancing antibody persistence after vaccination with a SARS-CoV-2 adenovirus vector vaccine, comprising Escherichia coli as an active ingredient, is provided. The SARS-CoV-2 adenovirus vector vaccine may preferably be ChAdOx1.

[0042] The above E. coli may preferably have 16s rRNA represented by sequence number 6.

[0043] According to another embodiment of the present invention, an adjuvant composition for enhancing an immune response upon SARS-CoV-2 vaccine booster vaccination is provided, comprising as an active ingredient at least one microorganism selected from the group consisting of Faecalibacterium prausnitzii, Peptoniphilus duerdenii, Mogibacterium genus JR_s, Ruminococcaceae genus PAC001048_s, and Anaerococcus provencensis.

[0044] The above Peptoniphilus duerdenii preferably has 16s rRNA represented by SEQ ID NO: 7, the above Mogibacterium genus JNA_s preferably has 16s rRNA represented by SEQ ID NO: 8, the above Ruminococcaceae genus PAC001048_s preferably has 16s rRNA represented by SEQ ID NO: 9, and the above Anaerococcus provencensis preferably has 16s rRNA represented by SEQ ID NO: 10.

[0045] The term "vaccine adjuvant," as used herein, refers to a substance administered together with a vaccine antigen to non-specifically enhance the immune response to the antigen. The composition of the present invention may be administered together with or separately from an existing vaccine to serve as an adjuvant that enhances the immunogenicity of the vaccine. The timing of administration is not limited, but is preferably administered prior to a SARS-CoV-2 vaccine booster vaccination, and most preferably at least one day prior to the booster vaccination.

[0046] As used herein, the term "enhanced immune response" refers to a stronger and more effective antibody response following a booster dose of a coronavirus (SARS-CoV-2) vaccine. Specifically, this can be assessed by the quantitative increase in neutralizing antibodies generated through the booster dose.

[0047] According to one aspect, the SARS-CoV-2 vaccine may be an mRNA vaccine, preferably BNT162b2.

[0048] According to another embodiment of the present invention, there is provided a method comprising the steps of: preparing biological samples separated from a plurality of subjects of at least two different groups;

[0049] A step of analyzing a microbial community from the above sample using LEfSe (linear discriminant analysis (LDA) Effect Size);

[0050] A step of predicting that, as a result of LEfSe analysis, if the LDA score of any one or more microorganisms among Faecalibacterium prausnitzii, Prevotella genus microorganisms, Gemmiger formicilis, and Bacteroides dorei in a specific group is 2.0 or higher, the subject belonging to that group will have better antibody durability after SARS-CoV-2 mRNA vaccination than the subject belonging to another group;

[0051] A method for providing personalized vaccination information to a subject, including:

[0052] According to one side, the good antibody durability may mean that the antibody half-life between 3 weeks and 6 months after the second vaccination is longer than the median of the cohort.

[0053]

[0054] Through our research, the inventors discovered that the impact of the gut microbiota on the durability and booster effect of vaccine immune responses may vary depending on the vaccine platform. Specifically, we identified that the microbial community that positively influences antibody persistence for an mRNA vaccine (BNT162b2) differs from that for an adenovirus vector vaccine (ChAdOx1).

[0055] Specifically, in the case of mRNA vaccines, microorganisms with a high ability to produce short-chain fatty acids (SCFAs), particularly butyrate, were shown to play a key role in extending antibody persistence. Faecalibacterium prausnitzii is the most representative butyrate-producing bacteria, and in the present study, it was observed in a significantly higher abundance in the group with a long antibody half-life after mRNA vaccination. In addition, other SCFA-producing bacteria belonging to the genera Prevotella, Bacteroides, and the families Ruminococcaceae and Lachnospiraceae were also associated with extended antibody persistence. SCFAs are known to enhance antibody responses by activating B cell metabolism, promoting differentiation into plasma cells, and regulating the expression of genes essential for antibody production. In particular, it promotes the differentiation and function of follicular helper T cells (Tfh), contributing to the production of high-affinity antibodies and inducing long-term humoral immune responses.

[0056] In contrast, for adenovirus vector vaccines, the abundance of Escherichia coli was significantly associated with prolonged antibody persistence. E. coli secretes molecules with potent immunostimulatory properties, effectively activating dendritic cells (DCs). Activated DCs can induce T and B cell activation, triggering a robust and sustained immune response. Given that the quantitative and qualitative activity of DCs may be particularly important in the immune response induction process of adenovirus vector vaccines, this suggests the existence of different mechanisms of microbe-immune interactions across vaccine platforms.

[0057] Even more noteworthy is the dual role of Faecalibacterium prausnitzii. This microorganism not only prolonged antibody persistence after the first dose of the mRNA vaccine, but was also significantly enriched in groups with high immune responses following the booster vaccination. This provides strong evidence that F. prausnitzii may positively influence both long-term immune memory formation (long-lived plasma cells) and rapid reactivation immune responses (memory B cells). Functional analysis using shotgun sequencing revealed that the high-responder group enriched in F. prausnitzii had significantly higher activity of 3-dehydroquinate synthase (EC: 4.2.3.4), an enzyme involved in the aromatic amino acid biosynthesis pathway. This pathway is present only in microorganisms and plants, not animals, and is known to play a crucial role in regulating the initial immune response. This provides a mechanistic explanation for how F. prausnitzii can modulate vaccine immune responses at the cellular level by activating a specific metabolic pathway.

[0058]

[0059] Hereinafter, embodiments are described in detail with reference to the attached drawings. However, the embodiments may be modified in various ways, and the scope of the patent application is not limited or restricted by these embodiments. It should be understood that all modifications, equivalents, or alternatives to the embodiments are included within the scope of the patent application.

[0060] The terms used in the examples are for illustrative purposes only and should not be construed as limiting. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as "comprise" or "have" are intended to specify the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, but should be understood to not preclude the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0061] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which the embodiments pertain. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and shall not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0062] In addition, when describing with reference to the attached drawings, identical components will be assigned the same reference numerals regardless of the drawing numbers, and redundant descriptions thereof will be omitted. When describing embodiments, if a detailed description of a related known technology is judged to unnecessarily obscure the gist of the embodiment, the detailed description will be omitted.

[0063]

[0064] Example 1: Research design and methods

[0065] 1-1. Research design and participants

[0066] This study was a prospective cohort study of 44 healthy adults who had completed the first dose of BNT162b2 or ChAdOx1 vaccine and were about to receive the second dose. Participants were divided into a two-dose BNT162b2 cohort (BNT162b2 cohort, n=23) and a two-dose ChAdOx1 cohort (ChAdOx1 cohort, n=21). Six months after completing the first dose series, all participants received a booster dose of the BNT162b2 vaccine. Fecal and blood samples were collected at four time points: V1 (just before the second dose), V2 (3 weeks after the second dose), V3 (6 months after the second dose and just before the booster dose), and V4 (3 weeks after the booster dose). Participants taking medications that could affect the gut microbiota, such as antibiotics, or having a history of SARS-CoV-2 infection were excluded from the study.

[0067]

[0068] 1-2. Group classification according to immune response

[0069] Serum anti-S (Spike) protein antibody titers were measured using the Elecsys® Anti-SARS-CoV-2 S assay kit (Roche). The half-life of anti-S antibodies was calculated based on antibody titer data at time points V2 and V3. Within each vaccine cohort (BNT162b2 and ChAdOx1), participants were classified into the “slow-decay group” and the “fast-decay group” based on the median antibody half-life. The acute antibody response after booster vaccination was assessed as the fold-change in antibody titer from V3 to V4, and subjects were classified into “high responders” and “low responders” based on the median fold-change (34-fold) of all booster recipients.

[0070]

[0071] 1-3. Microbiological analysis method

[0072] Total DNA was extracted from fecal samples using the FastDNA® SPIN Kit for Soil (MP Biomedicals). PCR amplification was performed using fusion primers targeting the V3-V4 region of the 16S rRNA gene, and the base sequence was analyzed using the Illumina MiSeq sequencing system. Shotgun sequencing was performed using the NEBNext Ultra II FS DNA Library Prep Kit to construct libraries and the NextSeq 1000 system. Bioinformatics analysis was performed using the EzBioCloud pipeline and HUMAnN, including taxonomic and functional profiling. Significant taxonomic and functional biomarkers between groups were identified using the linear discriminant analysis effect size (LEfSe) method, and an LDA score of 2.0 or higher was considered significant.

[0073]

[0074] Example 2: Microbiological analysis associated with antibody persistence after administration of mRNA vaccine (BNT162b2)

[0075] The BNT162b2 cohort was divided into groups based on antibody half-life after the second vaccination and the gut microbiota was analyzed. Alpha diversity analysis revealed that, at 3 weeks after the second vaccination (V2), the slow-decay group had significantly higher species richness (ACE index, p=0.035) and diversity (Simpson's index, p=0.035) than the fast-decay group (see Figure 1). This suggests that high microbial diversity early after the second vaccination may be associated with long-term antibody persistence.

[0076] LEfSe analysis identified specific microbial species significantly enriched in the slow-decay group. The results are shown in Table 1.

[0077] 분류군명분류LDA 효과 크기p-값Faecalibacterium prausnitziiBacteria: Firmicutes: Clostridia: Clostridiales: Ruminococcaceae: Faecalibacterium4.261750.04095Prevotella_ucBacteria: Bacteroidetes: Bacteroidia: Bacteroidales: Prevotellaceae: Prevotella4.254880.00819PAC001304_sBacteria: Bacteroidetes: Bacteroidia: Bacteroidales: Prevotellaceae: Prevotella4.159070.04801Gemmiger formicilisBacteria: Firmicutes: Clostridia: Clostridiales: Ruminococcaceae: Subdoligranulum3.917760.03896Bacteroides doreiBacteria: Bacteroidetes: Bacteroidia: Bacteroidales: Bacteroidaceae: Bacteroides3.718840.01251Agathobacter rectalisBacteria: Firmicutes: Clostridia: Clostridiales: Lachnospiraceae: Agathobacter3.497430.04703PAC001173_sBacteria: Firmicutes: Clostridia: Clostridiales: Ruminococcaceae:Subdoligranulum3.149410.04366PAC000195_sBacteria: Firmicutes: Clostridia: Clostridiales: Lachnospiraceae:PAC000195_g3.14060.0476JPJG_sBacteria: Firmicutes: Clostridia: Clostridiales: Ruminococcaceae:Oscillibacter3.019130.04765

[0078]

[0079] As shown in Table 1, Faecalibacterium prausnitzii showed the highest LDA score and a strong correlation with antibody persistence. Additionally, several microorganisms known to produce SCFAs, including two species of the genus Prevotella (Prevotella_uc, PAC001304_s), Gemmiger formicilis, Bacteroides dorei, and Agathobacter rectalis, were significantly abundant in the slow-decay group. Spearman correlation analysis also showed a significant positive correlation between the abundance of these microorganisms and antibody half-life.

[0080]

[0081] Example 3: Microbiological analysis associated with antibody persistence after administration of adenovirus vector vaccine (ChAdOx1)

[0082] The ChAdOx1 cohort showed different results from the BNT162b2 cohort. No significant differences in alpha and beta diversity were found between groups. However, LEfSe analysis identified Escherichia coli as the only significant biomarker in the slow-decay group (LDA effect size: 3.85796, p=0.00937). Spearman correlation analysis also showed that E. coli abundance was significantly positively correlated with antibody half-life. This result clearly demonstrates that the types of gut microbes that influence antibody persistence may vary depending on the vaccine platform.

[0083]

[0084] Example 4: Analysis of microorganisms associated with high immune responses after booster vaccination (BNT162b2)

[0085] All participants received a BNT162b2 booster vaccination, and were divided into high- and low-response groups based on the multiple increase in antibody titer. The gut microbiota was analyzed immediately prior to booster vaccination (V3). 16S rRNA sequencing and shotgun sequencing analyses revealed that specific microorganisms were significantly enriched in the high-response group. The results are presented in Table 2 and Figure 3.

[0086] Taxon NameClassLDA Effect Sizep-ValueFaecalibacterium prausnitziiBacteria: Firmicutes: Clostridia: Clostridiales: Ruminococcaceae:Faecalibacterium4.405390.03998Peptoniphilus duerdeniiBacteria: Firmicutes: Tissierellia: Tissierellales: Peptoniphilaceae:Peptoniphilus2.985480.03822JRNA_sBacteria: Firmicutes: Clostridia: Clostridiales: Mogibacterium_f:JRNA_g2.302960.04727PAC001048_sBacteria: Firmicutes: Clostridia: Clostridiales: Ruminococcaceae:PAC000672_g2.181110.02423Anaerococcus provencensisBacteria: Firmicutes: Tissierellia: Tissierellales: Peptoniphilaceae:Anaerococcus2.162540.01913

[0087]

[0088] As shown in Table 2 above, Faecalibacterium prausnitzii also showed the strongest association with booster vaccination response. Shotgun sequencing analysis also revealed that the relative abundance of F. prausnitzii in the high-response group (2.8%) was significantly higher than that in the low-response group (1.05%) (Fig. 3). This suggests that F. prausnitzii may play a key role not only in antibody persistence after the primary vaccination but also in enhancing immune memory responses during booster vaccination.

[0089]

[0090] Example 5: Functional Gene Analysis Associated with High Booster Response

[0091] Functional analysis using shotgun sequencing data identified specific metabolic pathways and genes enriched in the high-boost response group. The results are presented in Table 3.

[0092] DatabaseMarker IDDefinitionLDA Effect SizeP-ValueOrthologK02518Translation Initiation Factor IF-12.58930.0433OrthologK01358ATP-dependent Clp protease, protease subunit2.51340.0341OrthologK03702Excinuclease ABC subunit B2.1870.0433EC2.1.1.37DNA (cytosine-5-)-methyltransferase2.48180.1208EC4.2.3.43-dehydroquinate synthase2.39750.1199

[0093]

[0094] As shown in Table 3, the high-response group was enriched in genes involved in maintaining and regulating fundamental cellular functions, such as protein synthesis and DNA damage repair. In particular, 3-dehydroquinate synthase (EC: 4.2.3.4), an enzyme involved in the early step of the aromatic amino acid biosynthetic pathway, and DNA methylase (EC: 2.1.1.37), an enzyme involved in gene expression regulation, were found to be abundant in the high-response group. This, combined with the abundance of F. prausnitzii identified in Example 4, provides mechanistic evidence that this microorganism can modulate immune responses at the cellular level by activating specific metabolic pathways.

[0095]

[0096] Jejeye

[0097] Preparation Example 1: Manufacturing of health functional food capsules

[0098] Faecalibacterium prausnitzii and Prevotella_uc identified in the above Example 2 were cultured in large quantities under anaerobic conditions, and then centrifuged to recover the cells. The recovered cells were mixed with a cryoprotectant and freeze-dried to obtain each cell powder. 50 mg of freeze-dried powder of Faecalibacterium prausnitzii and 50 mg of freeze-dried powder of Prevotella_uc were uniformly mixed with 150 mg of microcrystalline cellulose and 5 mg of magnesium stearate, and then filled into a standard gelatin capsule to produce one capsule.

[0099]

[0100] Preparation Example 2: Preparation of freeze-dried powder for vaccine adjuvant

[0101] Faecalibacterium prausnitzii, identified in Example 4, was mass-cultured under anaerobic conditions and purified to obtain a high-concentration cell suspension. This suspension was aseptically filtered, a cryoprotectant was added, dispensed into vials, and lyophilized to produce a sterile lyophilized powder. The prepared vials can be resuspended in sterile water for injection or saline solution for oral administration during vaccination, or can be used as a formulation that can be administered together with a vaccine.

[0102]

[0103] Although the embodiments described above have been described with limited drawings, those skilled in the art will appreciate that various technical modifications and variations can be applied based on the above. For example, appropriate results can still be achieved even if the described techniques are performed in a different order than described, and / or components of the described systems, structures, devices, circuits, etc. are combined or combined in a different manner than described, or are replaced or substituted with other components or equivalents.

[0104] Therefore, other implementations, other embodiments, and equivalents to the claims also fall within the scope of the claims described below.

Claims

1. A health functional food composition for enhancing antibody persistence after SARS-CoV-2 mRNA vaccination, comprising as an active ingredient one or more microorganisms selected from the group consisting of Faecalibacterium prausnitzii, Prevotella microorganisms, Gemmiger formicilis, and Bacteroides dorei.

2. A composition according to claim 1, wherein the microorganism of the genus Prevotella is Prevotella_uc or PAC001304_s.

3. A composition according to any one of claims 1 and 2, characterized in that the composition is formulated in the form of a capsule, powder, tablet, or liquid.

4. A health functional food composition for enhancing antibody persistence after vaccination with a SARS-CoV-2 adenovirus vector vaccine, comprising Escherichia coli as an active ingredient.

5. A composition according to claim 4, characterized in that the composition is formulated in the form of a capsule, powder, tablet or liquid.

6. An adjuvant composition for enhancing an immune response to a SARS-CoV-2 vaccine booster vaccination, comprising as an active ingredient at least one microorganism selected from the group consisting of Faecalibacterium prausnitzii, Peptoniphilus duerdenii, Mogibacterium genus JR_s, Ruminococcaceae genus PAC001048_s, and Anaerococcus provencensis.

7. A composition according to claim 6, characterized in that the SARS-CoV-2 vaccine is an mRNA vaccine.

8. A step of preparing biological samples separated from multiple subjects of at least two different groups; A step of analyzing a microbial community from the above sample using LEfSe (linear discriminant analysis (LDA) Effect Size); A step of predicting that, as a result of LEfSe analysis, if the LDA score of any one or more microorganisms among Faecalibacterium prausnitzii, Prevotella genus microorganisms, Gemmiger formicilis, and Bacteroides dorei in a specific group is 2.0 or higher, the subject belonging to that group will have better antibody durability after SARS-CoV-2 mRNA vaccination than the subject belonging to another group; A method for providing personalized vaccination information to a subject, comprising:

9. A method for providing personalized vaccination information for a subject, wherein, in paragraph 8, the antibody durability is good in that the antibody half-life between 3 weeks and 6 months after the second vaccination is longer than the median of the cohort.

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