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@#Objective To prepare recombinant F protein vaccine of respiratory syncytial virus(RSV) and evaluate its immunization effect.Methods Two RSV vaccines based on RSV F protein were prepared:one was a mucosal vaccine with bacterial like particle(BLP)as adjuvant and the other was an injectable vaccine with aluminium hydroxide as adjuvant.Forty female BALB/c mice were randomly divided into four groups:BLP-F,BLP control,AL-F and AL control group,with 10mice in each group.BLP-F and BLP control group were inoculated intranasally,and AL-F and AL control group were inoculated subcutaneously.The mice were immunized once each at day 0,14 and 28,respectively.Two weeks after the last immunization,the titers of serum IgG antibody and IgA antibody in nasal lotion were detected by ELISA,and the titers of neutralizing antibody were detected by plaque test.Results Both vaccines induced high levels of serum binding antibodies and neutralizing antibodies,and the induction capacity of injected vaccine was stronger than that of mucosal vaccine.The injected vaccine induced the increase of IgG in serum,which was about 10 times higher than the mucosal immune response,but could not induce the increase of IgA.However,the mucosal vaccine induced the high level of mucosal IgA,but the serum IgG antibody was relatively low.Conclusion Both vaccines based on RSV F protein are promising candidates,and each vaccine has its own advantages.Follow-up studies will evaluate the feasibility of these two vaccines as immunogens using a combination immunization approach to simultaneously enhance systemic and mucosal immune responses against RSV.
ABSTRACT
COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.
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OBJECTIVE: Mucosal surfaces are a major portal of entry for many human pathogens that are the cause of infectious diseases. Vaccines that immunize by mucosal routes may induce protective immunity against mucosal pathogens at their sites of entry thus to be more effective and economical. We try to overview the status and progress of research on mucosal vaccines. METHODS: The databases of CNKI and Pubmed were used to search the related articles about mucosal vaccines with key words "mucosal vaccine, mucosal adjuvant, mucosal particulate delivery vectors" in Chinese and English. Articles closely related to mucosal vaccines were selected. RESULTS: Thirty-six articles were included at last. Live-attenuated or inactivated mucosal vaccines and vaccines based on new concepts such as subunit vaccines, virus-like particles and virosomes have been marketed, and related research work are undergoing. Safe and effective mucosal adjuvants and delivery vectors are being sought to enhance the magnitude and quality of the protective immune response. The composition, size, surface chemistry and ligands of particulate carrier systems may influence the efficacy. Great progress has been made in several particulate delivery systems. CONCLUSION: Although the research and development of mucosal vaccines are facing many difficulties and challenges, the progress of research work will bring new opportunities to mucosal vaccines development.
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Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases.
Subject(s)
Animals , Humans , Dendritic Cells/immunology , Immunity, Mucosal , Intestinal Mucosa/cytology , T-Lymphocytes, Helper-Inducer/immunologyABSTRACT
Objective To study the mucosal and systemic immune response after intranasal immunization with mucosal complex vaccine for Toxoplasma gondii,and to observe the protective effect on mice. Methods The mucosal complex vaccine was made of soluble tachyzoite antigen (STAg) and cholera toxin (CT),which were mixed and dissolved in PBS (1 ml PBS containing 1 mg STAg and 50 ?g CT). Fifty-two BALB/c mice were randomly divided into two groups: immunized group and control. Mice were intranasally immunized with 20 ?l mucosal complex vaccine (20 ?g STAg and 1?g CT) per mouse twice at an interval of two weeks,while the control mice were given PBS solution instead. Six mice of each group were killed by dislocation of cervical vertebra on day 14 after the last immunization. The specific IgG antibodies in serum and IgA in feces were detected by ELISA. Lymphocytes in spleen,Peyer's patches (PP) and intestinal intraepithelial lymphocyte(IEL) were isolated and counted. Percentage of CD4+ and CD8+ T cells was determined by immunocytochemistry. Other mice were challenged intragastrically each with 4?104 tachyzoites of RH strain Toxoplasma gondii on day 14 after the last immunization. Their health condition was observed and the number of tachyzoites in liver and brain was determined microscopically on the 30 th day after challenge. Results IgG antibodies in serum and IgA antibodies in feces of immunized mice were higher than the control (P