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The air temperature was critical to human health, especially for the mucosal immunity of the respiratory system. Amongst a few biomarkers, immunoglobulin was an effective material to evaluate respiratory health. In order to explore the effects of the natural air temperature on serum immunoglobulin concentrations of people, an epidemiological investigation was conducted between Jan 2018 and Dec 2019. In addition, an experiment was conducted to find the relationship between indoor air temperature and salivary immunoglobulin E (IgE) concentration, under the built environment within the comfort zone of people. Results of the epidemiological investigation showed that the serum IgE concentration was the most sensitive to temperature and was positively correlated with outdoor environmental temperature (p < 0.001, Spearman = 0.509). In addition, the experimental results showed that the salivary IgE concentration was also positively correlated with indoor temperature (p = 0.009, Spearman = 0.495), and it rose significantly with the increase of thermal comfort votes (p = 0.022, Spearman = 0.508). In a comfortable temperature range, keeping a higher air temperature can increase the concentration of IgE antibodies, which is one of the ways to improve the mucosal immunity of the respiratory system. [ABSTRACT FROM AUTHOR]

Background: There is a need for vaccines that can induce effective systemic, respiratory mucosal, and cellular immunity to control the COVID‐19 pandemic. We reported previously that a synthetic mucosal adjuvant SF‐10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen‐specific serum IgG, mucosal IgA, and cellular immunity. Methods: The aim of the present study was to determine the effectiveness of a new administration route of trans‐airway (TA) vaccine comprising recombinant SARS‐CoV‐2 spike protein 1 (S1) combined with SF‐10 (S1‐SF‐10 vaccine) on systemic, local, and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AddaS03™ (S1‐AddaS03™ vaccine). Results: S1‐SF‐10‐TA vaccine induced S1‐specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1‐SF‐10‐TA showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS‐CoV‐2, which were more potent and faster achievement than S1‐AddaS03™‐IM. Enzyme‐linked immunospot assay showed high numbers of S1‐specific IgA and IgG secreting cells (ASCs) and S1‐responsive IFN‐γ, IL‐4, IL‐17A cytokine secreting cells (CSCs) in the spleen and lungs. S1‐AddaS03™‐IM induced IgG ASCs and IL‐4 CSCs in spleen higher than S1‐SF‐10‐TA, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusions: Based on the need for effective systemic, respiratory, and cellular immunity, the S1‐SF‐10‐TA vaccine seems promising mucosal vaccine against respiratory infection of SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Mucosal vaccines can prevent viruses from infecting the respiratory mucosa, rather than only curtailing infection and protecting against the development of disease symptoms. The SARS-CoV-2 spike receptor-binding domain (RBD) is a compelling vaccine target but is undermined by suboptimal mucosal immunogenicity. Here, we report a SARS-CoV-2-mimetic extracellular-vesicle vaccine developed using genetic engineering and dendritic cell membrane budding. After mucosal immunization, the vaccine recruits antigen-presenting cells rapidly initiating a strong innate immune response. Notably, it obviates the need for adjuvants and can induce germinal center formation through both intramuscular and intratracheal vaccination. It not only elicits high levels of RBD-specific antibodies but also stimulates extensive cellular immunity in the respiratory mucosa. A sequential immunization strategy, starting with an intramuscular injection followed by an intratracheal booster, significantly bolsters mucosal immunity with high levels of IgA and tissue-resident memory T cell responses, thereby establishing a formidable defense against pseudovirus infection.

Malnutrition is associated with a state of secondary immunodeficiency, which is characterized by a worsening of the immune response against infectious agents. Despite important advances in vaccines and antibiotic therapies, the respiratory infections are among the leading causes of increased morbidity and mortality, especially in immunosuppressed hosts. In this review, we examine the interactions between immunobiotics-postbiotics and the immune cell populations of the respiratory mucosa. In addition, we discuss how this cross talk affects the maintenance of a normal generation of immune cells, that is crucial for the establishment of protective innate and adaptive immune responses. Particular attention will be given to the alterations in the development of phagocytic cells, T and B lymphocytes in bone marrow, spleen and thymus in immunosuppression state by protein deprivation. Furthermore, we describe our research that demonstrated that the effectiveness of immunobiotics nasal administration in accelerating the recovery of the respiratory immune response in malnourished hosts. Finally, we propose the peptidoglycan from the immunobiotic Lactobacillus rhamnosus CRL1505 as the key cellular component for the effects on mucosal immunity, which are unique and cannot be extrapolated to other L. rhamnosus or probiotic strains. In this way, we provide the scientific bases for its application as a mucosal adjuvant in health plans, mainly aimed to improve the immune response of immunocompromised hosts. The search for safe vaccine adjuvants that increase their effectiveness at the mucosal level is a problem of great scientific relevance today.

The purpose of this study is to investigate the effect of draught on upper respiratory tract mucosal immunity, by assessing concentrations of lysozyme and secretory immunoglobulin A (S-IgA) in nasal lavage fluid. A total of 26 subjects were recruited and experienced 4 experiment conditions combined with two ambient temperatures (24 °C and 28 °C) and two air velocities towards the nape (0 m/s and 1 m/s). Physiological parameters, and subjective questionnaires (i.e., thermal sensation vote (TSV), thermal comfort vote (TCV), and air movement vote (AMV)) were also collected. Our findings revealed that physiological parameters fluctuated significantly under 24 °C, 1 m/s (p < 0.05). Significant decreases in lysozyme concentration occurred under both 24 °C, 1 m/s (p = 0.003) and 24 °C, 0 m/s (p = 0.017). S-IgA concentrations significantly decreased after one-day lag (p = 0.028) under 24 °C, 1 m/s. When TSV deviated from neutral, lysozyme concentrations decreased, especially when the TSV was [-3, −1.5) (p = 0.01). The S-IgA concentration increased when subjects felt slightly uncomfortable and decreased steadily for further discomfort. The proportion of subjects with decreased immune biomarker levels was minimized in the neutral TSV zone. The findings suggest that under the investigated scenarios, cold draught can suppress respiratory immunity by altering thermal sensations, with effects potentially persisting beyond exposure duration. Ensuring a neutral and comfortable thermal environment is pivotal for maintaining immunity stability. However, more experiments under a wider range of thermal parameters need to be performed to prove the robustness of current results. • Lysozyme level decreased when the result of thermal sensation votes deviated from neutral zone. • S-IgA level fluctuates when the result of thermal comfort votes deviated from comfortable zone. • The proportion of subjects whose immune level decreased was least with neutral thermal sensation. • The effect of cold draught on respiratory immunity may last for more than one day. • Respiratory immunity remains stable in neutral and comfortable thermo-environments. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the link between temperature-induced comfort and salivary secretory immunoglobulin E (S-IgE), a biomarker used to assess respiratory mucosal immunity. Our findings revealed that the highest S-IgE concentration occurred at 24 °C, close to the thermal neutral temperature of 22.7 °C in the thermal neutral temperature range of 21.4–26.9 °C, regardless of exposure time (5 or 30 min); However, after 60 min of exposure, when the ambient temperature increased from 21 to 33 °C, the subjects' average thermal sensation vote (TSV) and S-IgE concentration gradually increased by 3.2 units and 62.8%, respectively, compared to 21 °C; Moreover, as the TSV increased from slightly cool to warm, the S-IgE concentration corresponding to the TSV (+1.5, +3] and [- 3, - 1.5) increased by 60.6% and 11.4%, respectively, compared to [- 1.5, - 0.5) and (+0.5, +1.5], respectively. We propose that comfortable ambient temperature can only increase the concentration of S-IgE for a short time (30 min), while prolonged cold and heat exposure (60 min) is more conducive to increasing the S-IgE concentration, which may improve respiratory mucosa immunity to some extent. • Temperature and exposure time significantly affected thermal comfort and S-IgE level. • Temperature and time affected the relationship between thermal comfort and S-IgE level. • The S-IgE was more sensitive to cold exposure than to heat exposure. • After 30min exposure, the S-IgE level showed two peaks with the increasing thermal sensation. • After 60min exposure, the S-IgE level increased with the increasing the thermal sensation vote. [ABSTRACT FROM AUTHOR]

The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC. [Display omitted] • Two trivalent adenoviral-vectored COVID-19 vaccines were developed and evaluated • Intranasal, but not intramuscular, immunization induces tripartite mucosal immunity • Intranasal immunization protects against ancestral and variant strains of SARS-CoV-2 • Optimal protection requires B and T cell immunity and trained innate immunity Respiratory mucosal immunization with a next-generation adenoviral-vectored trivalent COVID-19 vaccine expressing spike, nucleocapsid, and RdRp antigens, induces all-around protective mucosal immunity against SARS-CoV-2 via induction of systemic and local antibodies, lung-tissue-resident memory T cells, and trained alveolar macrophages. [ABSTRACT FROM AUTHOR]

• The bionic-virus nanovaccine completely simulated the structure of SARS-CoV-2. • The nanovaccine induced innate immunity by stimulating TLR 3 pathway. • The bio-PS layer liposomes could effectively enter into alveolar epithelial cells. • The nanovaccine was delivered easily and painlessly through respiratory route. • Nasal administration induced strong respiratory mucosal immunity. The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through "respiratory droplets". Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to prevent virus infection from respiratory tract. The nanovaccine that mimic virosome is composed of poly(I:C) mimicking viral genetic material as immune adjuvant, biomimetic pulmonary surfactant (bio-PS) liposomes as capsid structure of virus and the receptor binding domains (RBDs) of SARS-CoV-2 as "spike" to completely simulate the structure of the coronavirus. The nanovaccine can be administered by inhaling to imitate the process of SARS-CoV-2 infection through the respiratory tract. Our results demonstrated that the inhalable nanovaccine with bionic virus-like structure has a stronger mucosal protective effect than routine muscle and subcutaneous inoculation. In particular, high titer of secretory immunoglobulin A (sIgA) was detected in respiratory secretions, which effectively neutralize the virus and prevent it from entering the body through the respiratory tract. Through imitating the structure and route of infection, this inhalable nanovaccine strategy might inspire a new approach to the precaution of respiratory viruses. [ABSTRACT FROM AUTHOR]

The respiratory tract of children in the first two years of life, unlike that of adults, contains bronchus-associated lymphoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) with no differences in frequency between SID and control children. Using immunohistochemical methods we examined the distribution of B, T, CD4+ and CD8+ lymphocytes, HLA-D+ cells, CD68+ macrophages and proliferating cells, comparing bronchus-associated and larynx-associated lymphoid tissue of sudden infant death cases and controls. In all groups the lymphoid tissue was organized in lymphoid follicles and parafollicular areas. With no differences in the cellular composition of BALT and LALT the lymphoid follicles contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably T lymphocytes of both subset types and B lymphocytes were observed in equal numbers in the parafollicular areas in contrast to gut-associated lymphoid tissue. However, the respiratory tract of young children with no differences between SID and controls might play a similar role in mucosal immunity and might function as an inductive site. [ABSTRACT FROM AUTHOR]

Malnutrition is associated with a state of secondary immunodeficiency, which is characterized by a worsening of the immune response against infectious agents. Despite important advances in vaccines and antibiotic therapies, the respiratory infections are among the leading causes of increased morbidity and mortality, especially in immunosuppressed hosts. In this review, we examine the interactions between immunobiotics-postbiotics and the immune cell populations of the respiratory mucosa. In addition, we discuss how this cross talk affects the maintenance of a normal generation of immune cells, that is crucial for the establishment of protective innate and adaptive immune responses. Particular attention will be given to the alterations in the development of phagocytic cells, T and B lymphocytes in bone marrow, spleen and thymus in immunosuppression state by protein deprivation. Furthermore, we describe our research that demonstrated that the effectiveness of immunobiotics nasal administration in accelerating the recovery of the respiratory immune response in malnourished hosts. Finally, we propose the peptidoglycan from the immunobiotic Lactobacillus rhamnosus CRL1505 as the key cellular component for the effects on mucosal immunity, which are unique and cannot be extrapolated to other L. rhamnosus or probiotic strains. In this way, we provide the scientific bases for its application as a mucosal adjuvant in health plans, mainly aimed to improve the immune response of immunocompromised hosts. The search for safe vaccine adjuvants that increase their effectiveness at the mucosal level is a problem of great scientific relevance today., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Salva, Kolling, Ivir, Gutiérrez and Alvarez.)