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Vaccines Jun 2024Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity... (Review)
Review
Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5'cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases.
PubMed: 38932399
DOI: 10.3390/vaccines12060670 -
Vaccines Jun 2024Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2...
Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. In a previous study, a sublingual SARS-CoV-2 vaccination was created by combining a recombinafigureCoV-2 spike protein receptor-binding domain antigen with a double strand RNA Poly(I:C) adjuvant. This vaccine was tested on nonhuman primates, Cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvants, and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccine produced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines-IFN-alpha, IFN-gamma, and IL-17-in the blood, nor upregulated the gene expression of proinflammatory cytokines-IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B-in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with the Poly(I:C) adjuvant is safe, and creates a balanced state of enhancing and suppressing the immune-related response.
PubMed: 38932372
DOI: 10.3390/vaccines12060643 -
Viruses May 2024Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful...
Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful detection of SARS-CoV-2-specific nasal mucosal antibodies in a group of exposed-household individuals that evaded systemic infection. Between June 2020 and February 2023, nasopharyngeal swab (NPS) and acute and convalescent blood were collected from individuals exposed to a SARS-CoV-2-confirmed household member. Nasal secretory IgA (SIgA) antibodies targeting the SARS-CoV-2 spike protein were measured using a modified ELISA. Of the 36 exposed individuals without SARS-CoV-2 detected by the RT-PCR of NPS specimens and seronegative for SARS-CoV-2-specific IgG at enrollment and convalescence, 13 (36.1%) had positive SARS-CoV-2-specific SIgA levels detected in the nasal mucosa at enrollment. These individuals had significantly higher nasal SIgA (median 0.52 AU/mL) compared with never-exposed, never-infected controls (0.001 AU/mL) and infected-family participants (0.0002 AU/mL) during the acute visit, respectively (both < 0.001). The nasal SARS-CoV-2-specific SIgA decreased rapidly over two weeks in the exposed seronegative individuals compared to a rise in SIgA in infected-family members. The nasal SARS-CoV-2-specific SIgA may have a protective role in preventing systemic infection.
Topics: Humans; SARS-CoV-2; COVID-19; Immunoglobulin A, Secretory; Male; Female; Adult; Antibodies, Viral; Middle Aged; Antibodies, Neutralizing; Nasal Mucosa; Spike Glycoprotein, Coronavirus; Young Adult; Immunity, Mucosal; Aged; Immunoglobulin G
PubMed: 38932145
DOI: 10.3390/v16060852 -
Viruses May 2024Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral... (Review)
Review
Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.
Topics: Rotavirus Vaccines; Humans; Rotavirus Infections; Animals; Rotavirus; T-Lymphocytes; Administration, Oral; Immunity, Mucosal; Mice
PubMed: 38932111
DOI: 10.3390/v16060818 -
Pharmaceuticals (Basel, Switzerland) May 2024Microbicides, which are classified as topical antiseptic agents, are a revolutionary advancement in HIV prevention aimed to prevent the entry of infectious agents into... (Review)
Review
Microbicides, which are classified as topical antiseptic agents, are a revolutionary advancement in HIV prevention aimed to prevent the entry of infectious agents into the human body, thus stopping the sexual transmission of HIV and other sexually transmitted diseases. Microbicides represent the promise of a new age in preventive measures against one of the world's most pressing health challenges. In addition to their direct antiviral effects during HIV transmission, microbicides also influence vaginal mucosal immunity. This article reviews microbicides by presenting different drug classifications and highlighting significant representatives from each group. It also explains their mechanisms of action and presents information about vaginal mucosal immune responses, emphasizing the critical role they play in responding to HIV during sexual transmission. The article discusses the following groups of microbicides: surfactants or membrane disruptors, vaginal milieu protectors, anionic polymers, dendrimers, carbohydrate-binding proteins, HIV replication inhibitors (reverse transcriptase inhibitors), and multi-purpose prevention technologies, which combine protection against HIV, other sexually transmitted diseases, and contraception. For each chemical compound, the article provides a brief overview of relevant preclinical and clinical research, emphasizing their potential as microbicides. The article offers insights into the multifaceted impact of microbicides, which signify a pivotal step forward in the pursuit of effective and accessible pre-exposure prophylaxis (PrEP).
PubMed: 38931337
DOI: 10.3390/ph17060668 -
Microorganisms Jun 2024The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, () has relatively less...
The treatment and prevention of pathogenic diseases by lactic acid bacteria (LAB) has attracted more and more attention. As a special LAB, () has relatively less research on its antibacterial infection in vivo, and its protective effect and mechanism still need to be fully studied. In this study, we selected 23017, which can regulate the intestinal immunity of the host animal and resist pathogen infection, to evaluate its protective role and potential molecular mechanisms in the mouse model of C7731 infection. As expected, we confirmed that 23017 reduced the diarrhea rate and increased the daily weight gain and survival rate of the mouse model, and inhibited colonization in the jejunum and liver. It also reduced the level of oxidative damage and protected the integrity of intestinal tissue by increasing the activity of intestinal antioxidant enzymes (SOD, GSH-Px and T-AOC). From the perspective of intestinal mucosal barrier injury and repair, it was confirmed that 23017 could increase the expression levels of intestinal tight junction proteins (ZO-1 and OCLN). Our research results also show that 23017 inhibits the inflammatory response and promotes the occurrence of cellular immunity in the body by promoting the increase in IL-10 and inhibiting IL-13 in serum and intestinal tissue. Notably, 23017 increased total secretory immunoglobulin A (SIgA) levels in the intestine, which were closely associated with elevated levels of IL-5, IL-13, pIgR, j-chain, and IgAα-chain. In addition, 23017 increased the expression of antioxidant proteins Nrf2, NQO1, and HO-1 associated with Nrf2 signaling to inhibit intestinal oxidative damage. This mechanism may be responsible for its protective effect against -infected intestine. Our study provides new evidence and theoretical support for the analysis of the anti-bacterial infection effect and mechanism of , which will contribute to the development of and the treatment of pathogenic bacteria intestinal infection.
PubMed: 38930517
DOI: 10.3390/microorganisms12061135 -
Animals : An Open Access Journal From... Jun 2024This study assessed the impact of Magni-Phi Ultra (MPU) inclusion on intestinal integrity and immunity in broiler chickens challenged with coccidia during peak and...
This study assessed the impact of Magni-Phi Ultra (MPU) inclusion on intestinal integrity and immunity in broiler chickens challenged with coccidia during peak and recovery phases. A total of 128 male Ross 708 broiler chicks were randomly allotted to one of four treatment groups (four chicks/cage). Treatments included an uninfected control (UUC); a coccidial challenge (CC) infected control (IUC); a CC fed salinomycin at 66 ppm (SAL); and a CC fed Magni-Phi Ultra at 0.11 g/kg of diet (MPU). At 16 days post-hatch, all birds in the CC groups were orally gavaged with a 3× dose of a live coccidia vaccine. At 5 dpi, the birds fed MPU and SAL showed decreased plasma FITC-d, oocyte shedding, and lesion scores and higher BWG compared to the IUC birds ( < 0.05). Jejunum , , and - mRNA expression was higher in the IUC compared to the UUC ( < 0.05) group at 5 dpi. At 12 dpi, the birds fed MPU or SAL had lower plasma FITC-d and jejunum - and -10 mRNA expression compared to the IUC birds ( < 0.05). This study indicates that MPU supports intestinal integrity and mucosal immune responses during the peak and recovery phases of infection, which may lead to improved health and performance.
PubMed: 38929356
DOI: 10.3390/ani14121737 -
Microbiology and Immunology Jun 2024Agglutination of pathogenic microorganisms on the body surface is a significant phenomenon for the prevention of infection. In the present study, we show that an extract...
Agglutination of pathogenic microorganisms on the body surface is a significant phenomenon for the prevention of infection. In the present study, we show that an extract of the skin mucus from Japanese flounder (Paralichthys olivaceus) has agglutination activity against the yeast Saccharomyces cerevisiae. We purified this yeast-binding protein, which consists of an approximately 35-kDa homodimer, using affinity chromatography with yeast as a ligand. Multiple internal amino acid sequences of the protein, as determined using liquid chromatography with quadrupole time-of-flight tandem mass spectrometry, mapped to flounder glyceraldehyde 3-phosphate dehydrogenase (GAPDH). An anti-GAPDH antibody inhibited the yeast agglutination activity in the skin mucus extract and stained agglutinated yeast, indicating that flounder GAPDH could agglutinate yeast. The current study suggests that GAPDH, a well-known protein as the sixth enzyme in the glycolytic pathway, is a significant player in mucosal immunity in teleosts.
PubMed: 38923675
DOI: 10.1111/1348-0421.13163 -
ImmunoHorizons Jun 2024The underlying contribution of immune complexes in modulating adaptive immunity in mucosal tissues remains poorly understood. In this report, we examined, in mice, the...
The underlying contribution of immune complexes in modulating adaptive immunity in mucosal tissues remains poorly understood. In this report, we examined, in mice, the proinflammatory response elicited by intranasal delivery of the biothreat agent ricin toxin (RT) in association with two toxin-neutralizing mAbs, SylH3 and PB10. We previously demonstrated that ricin-immune complexes (RICs) induce the rapid onset of high-titer toxin-neutralizing Abs that persist for months. We now demonstrate that such responses are dependent on CD4+ T cell help, because treatment of mice with an anti-CD4 mAb abrogated the onset of RT-specific Abs following intranasal RICs exposure. To define the inflammatory environment associated with RIC exposure, we collected bronchoalveolar lavage fluid (BALF) and sera from mice 6, 12, and 18 h after they had received RT or RICs by the intranasal route. A 32-plex cytometric bead array revealed an inflammatory profile elicited by RT that was dominated by IL-6 (>1500-fold increase in BALF) and secondarily by KC (CXCL1), G-CSF, GM-CSF, and MCP-1. RICs induced inflammatory profiles in both BALF and serum response that were similar to RT, albeit at markedly reduced levels. These results demonstrate that RICs retain the capacity to induce local and systemic inflammatory cytokines/chemokines that, in turn, may influence Ag sampling and presentation in the lung mucosa and draining lymph nodes. A better understanding of the fate of immune complexes following intranasal delivery has implications for the development of mucosal vaccines for biothreats and emerging infectious diseases.
Topics: Animals; Administration, Intranasal; Ricin; Mice; Bronchoalveolar Lavage Fluid; Female; Antigen-Antibody Complex; Antibodies, Neutralizing; Immunization; Inflammation; Antibodies, Monoclonal; Cytokines; CD4-Positive T-Lymphocytes; Mice, Inbred BALB C; Mice, Inbred C57BL
PubMed: 38922287
DOI: 10.4049/immunohorizons.2400007 -
Communications Biology Jun 2024Innate lymphoid cells (ILCs) are largely tissue-resident, mostly described within the mucosal tissues. However, their presence and functions in the human draining lymph... (Comparative Study)
Comparative Study
Innate lymphoid cells (ILCs) are largely tissue-resident, mostly described within the mucosal tissues. However, their presence and functions in the human draining lymph nodes (LNs) are unknown. Our study unravels the tissue-specific transcriptional profiles of 47,287 CD127 ILCs within the human abdominal and thoracic LNs. LNs contain a higher frequency of CD127 ILCs than in BM or spleen. We define independent stages of ILC development, including EILP and pILC in the BM. These progenitors exist in LNs in addition to naïve ILCs (nILCs) that can differentiate into mature ILCs. We define three ILC1 and four ILC3 sub-clusters in the LNs. ILC1 and ILC3 subsets have clusters with high heat shock protein-encoding genes. We identify previously unrecognized regulons, including the BACH2 family for ILC1 and the ATF family for ILC3. Our study is the comprehensive characterization of ILCs in LNs, providing an in-depth understanding of ILC-mediated immunity in humans.
Topics: Humans; Immunity, Innate; Lymph Nodes; Lymphocytes; Spleen; Transcriptome; Bone Marrow; Gene Expression Profiling; Male
PubMed: 38918571
DOI: 10.1038/s42003-024-06450-9