mRNA-based COVID-19 vaccines have played a critical role in reducing severe outcomes of COVID-19. Humoral immune responses against SARS-CoV-2 after vaccination have been extensively studied in blood; however, limited information is available on the presence and duration of SARS-CoV-2 specific antibodies in saliva and other mucosal fluids. Saliva offers a non-invasive sampling method that may also provide a better understanding of mucosal immunity at sites where the virus enters the body. Our objective was to evaluate the salivary immune response after vaccination with the COVID-19 Moderna mRNA-1273 vaccine. Two hundred three staff members of the U.S. Centers for Disease Control and Prevention were enrolled prior to receiving their first dose of the mRNA-1273 vaccine. Participants were asked to self-collect 6 saliva specimens at days 0 (prior to first dose), 14, 28 (prior to second dose), 42, and 56 using a SalivaBio saliva collection device. Saliva specimens were tested for anti-spike protein SARS-CoV-2 specific IgA and IgG enzyme immunoassays. Overall, SARS-CoV-2-specific salivary IgA titers peaked 2 weeks after each vaccine dose, followed by a sharp decrease during the following weeks. In contrast to IgA titers, IgG antibody titers increased substantially 2 weeks after the first vaccine dose, peaked 2 weeks after the second dose and persisted at an elevated level until at least 8 weeks after the first vaccine dose. Additionally, no significant differences in IgA/IgG titers were observed based on age, sex, or race/ethnicity. All participants mounted salivary IgA and IgG immune responses against SARS-CoV-2 after receiving the mRNA-1273 COVID-19 vaccine. Because of the limited follow-up time for this study, more data are needed to assess the antibody levels beyond 2 months after the first dose. Our results confirm the potential utility of saliva in assessing immune responses elicited by immunization and possibly by infection.

Anticoccidial vaccines comprising living oocysts of Eimeria tenella, Eimeria necatrix, Eimeria maxima, and Eimeria acervulina are used to control coccidiosis. This study explored the potential of IL-1β to act as a molecular adjuvant for enhancing the immunogenicity of Eimeria necatrix and mucosal immunity. We engineered E. necatrix to express a functional chIL-1β (EnIL-1β) and immunized chickens with oocysts of the wild type (EnWT) and tranegenic (EnIL-1β) strains, respectively. The chickens were then challenged with EnWT oocysts to examine the immunogenicity-enhancing potential of chIL-1β. As expected, the oocyst output of EnIL-1β-immunized chickens was significantly reduced compared to those immunized using EnWT. No difference in body weight gain and lesion scores of EnIL-1β and EnWT groups was observed. The parasite load in the small intestine and caeca showed that the invasion and replication of EnIL-1β was not affected. However, the markers of immunogenicity and mucosal barrier, Claudin-1 and avian β-defensin-1, were elevated in EnIL-1β-infected chickens. Ectopic expression of chIL-1β in E. necatrix thus appears to improve its immunogenicity and mucosal immunity, without increasing pathogenicity. Our findings support chIL-1β as a candidate for development of effective live-oocyst-based anticoccidial vaccines.

Mucosal immunity plays a crucial role in defending against coronaviruses, particularly at respiratory sites, serving as the first line of defense against viral invasion and replication. Coronaviruses have developed various immune evasion strategies at the mucosal immune system, hindering the recognition of infected cells and evading antibody responses. Understanding the immune mechanisms and responses is crucial for developing effective vaccines and therapeutics against coronaviruses. The role of mucosal immunity in COVID-19 is significant, influencing both local and systemic immune responses to the virus. Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Mucosally delivered vaccines and those under clinical trials are being compared and contrasted to understand their effectiveness in inducing mucosal immunity against coronaviruses. A greater understanding of lung tissue-based immunity may lead to improved diagnostic and prognostic procedures and novel treatment strategies aimed at reducing the disease burden of community-acquired pneumonia, avoiding the systemic manifestations of infection and excess morbidity and mortality. This comprehensive review article outlines the current evidence about the role of mucosal immune responses in the clearance of SARS-CoV-2 infection, as well as potential mucosal mechanisms of protection against (re-)infection. It also proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes. The findings from recent studies on mucosal immunity in COVID-19 can be used to develop effective vaccines and treatments that can effectively target both mucosal and systemic immune responses.

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.

Microbiota-derived antigens play a critical role in the development of both the mucosal and systemic B cell repertoires; however, how glycan epitopes promote B cell repertoire selection is only recently being understood. The production of glycan-derived antigens by individual microbes within a host can be dynamic and influenced by interactions within other members of microbial communities, the composition of diet, and host-derived contents, including those of the mucosal immune system. The size and complexity of the emerging neonatal B cell repertoire are paralleled by the acquisition of a diverse microbiota from maternal and environmental sources, which is now appreciated to exert long-lasting influences on the nascent B cell repertoire.

The unconventional type I interferons IFNε and IFNω and type III interferon IFNλ are gradually emerging as tissue-specific cytokines in defence of mucosal tissues. This review provides an overview of the distinct features and functions that define these IFNs as protective factors in the respiratory, gastrointestinal and reproductive tracts, highlighting their immunoregulatory roles against pathogens while maintaining tolerance against commensal microbes. In particular, we discuss recent advances in our understanding of the constitutively expressed IFNε and its role in protecting against mucosal infections, inflammation and cancers. We identify an emerging theme for this unique cytokine as a key contributor to the \'first line of defence\' against pathogens and maintenance of mucosal tissue homeostasis, primarily through its regulation of immune cell populations.

Mucosal vaccination is a promising strategy for combating infectious diseases caused by pathogenic microbes, as it can generate antigen-specific immune responses in both systemic and mucosal compartments. In our recent study, we developed a nasal vaccine system for Streptococcus pneumoniae infections in mice using enzymatically polymerized polyphenols such as caffeic acid. However, the efficacy of this mucosal vaccine system is approximately 70%, indicating a need for improvement. To address this issue, we hypothesized that incorporating a mucoadhesive agent that enhances mucosal absorption into a polyphenol-based mucosal vaccine system would improve vaccine efficacy. Contrary to our expectations, we found that adding a mucoadhesive agent, hydrophobically modified hydroxypropylmethylcellulose, to the vaccine system reduced the stimulation of antigen-specific antibody responses in both the mucosal (more than 90% reduction; P < 0.05) and systemic compartments (more than 80% reduction; P < 0.05). Although the addition of the mucoadhesive agent may have interfered with the interaction between the mucosal epithelium and the vaccine system, the underlying mechanism remains unclear, and further research is needed to fully understand the mechanisms involved.

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Brucellosis is a chronic infectious disease that is zoonotic in nature. Brucella can infect humans through interactions with livestock, primarily via the digestive tract, respiratory tract, and oral cavity. This bacterium has the potential to be utilized as a biological weapon and is classified as a Category B pathogen by the Centers for Disease Control and Prevention. Currently, there is no approved vaccine for humans against Brucella, highlighting an urgent need for the development of a vaccine to mitigate the risks posed by this pathogen. Brucella primarily infects its host by adhering to and penetrating mucosal surfaces. Mucosal immunity plays a vital role in preventing local infections, clearing microorganisms from mucosal surfaces, and inhibiting the spread of pathogens. As mucosal vaccine strategies continue to evolve, the development of a safe and effective mucosal vaccine against Brucella appears promising.This paper reviews the immune mechanism of mucosal vaccines, the infection mechanism of Brucella, successful Brucella mucosal vaccines in animals, and mucosal adjuvants. Additionally, it elucidates targeting and optimization strategies for mucosal vaccines to facilitate the development of human vaccines against Brucella.

How group 3 innate lymphoid cells (ILC3s) regulate mucosal protection in the presence of T cells remains poorly understood. Here, we examined ILC3 function in intestinal immunity using ILC3-deficient mice that maintain endogenous T cells, T helper 17 (TH17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of TH17 and TH22 cell responses to commensal and pathogenic bacteria, and absence of ILC3s did not affect IL-22 production by CD4 T cells before or during infection. However, despite the presence of IL-22-producing T cells, ILC3s and ILC3-derived IL-22 were required for maintaining homeostatic functions of the intestinal epithelium. T cell-sufficient, ILC3-deficient mice were capable of pathogen clearance and survived infection with a low dose of Citrobacter rodentium. However, ILC3s promoted pathogen tolerance at early time points of infection by activating tissue-protective immune pathways. Consequently, ILC3s were indispensable for survival after high-dose infection. Our results demonstrate a context-dependent role for ILC3s in immune-sufficient animals and provide a blueprint for uncoupling of ILC3 and TH17 cell functions.