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Yellow fever (YF), caused by the yellow fever virus (YFV), continually spreads and causes epidemics worldwide, posing a great threat to human health. The live-attenuated YF 17D vaccine (YF-17D) has been licensed for preventing YFV infection and administrated via the intramuscular (i.m.) route. In this study, we sought to determine the immunogenicity and protective efficacy of aerosolized YF-17D via the intratracheal (i.t.) route in mice. YF-17D stocks in liquids were successfully aerosolized into particles of 6 μm. Further in vitro phenotype results showed the aerosolization process did not abolish the infectivity of YF-17D. Meanwhile, a single i.t. immunization with aerosolized YF-17D induced robust humoral and cellular immune responses in A129 mice, which is comparable to that received i.p. immunization. Notably, the aerosolized YF-17D also triggered specific secretory IgA (SIgA) production in bronchoalveolar lavage. Additionally, all immunized animals survived a lethal dose of YFV challenge in mice. In conclusion, our results support further development of aerosolized YF-17D in the future. [ABSTRACT FROM AUTHOR]

Background: Porcine reproductive and respiratory syndrome (PRRS) is a viral disease with worldwide distribution and an enormous economic impact. To control PRRS virus (PRRSV) infection, modified live vaccines (MLVs) are widely used in the field, mainly administered via an intramuscular (IM) route. Currently, some MLVs are authorized for intradermal (ID) administration, which has many practical and welfare advantages. The objectives of the study were to compare the immune responses (systemic in blood and mucosal in lungs) and vaccine efficacy in preventing challenge strain transmission after IM or needle-free ID immunization of piglets with an MLV against PRRSV-1 (MLV1). Methods: Groups of sixteen 5-week-old specific pathogen-free piglets were vaccinated with Porcilis PRRS® (MSD) either by an IM (V+ IM) or ID route (V+ ID) using an IDAL®3G device or kept unvaccinated (V-). Four weeks after vaccination, in each group, 8 out of the 16 piglets were challenged intranasally with a PRRSV-1 field strain, and one day later, the inoculated pigs were mingled by direct contact with the remaining 8 sentinel noninoculated pigs to evaluate PRRSV transmission. Thus, after the challenge, each group (V+ IM, V+ ID or V-) included 8 inoculated and 8 contact piglets. During the postvaccination and postchallenge phases, PRRSV replication (RT–PCR), PRRSV-specific antibodies (ELISA IgG and IgA, virus neutralization tests) and cell-mediated immunity (ELISPOT Interferon gamma) were monitored in blood and bronchoalveolar lavages (BALs). Results: Postvaccination, vaccine viremia was lower in V+ ID pigs than in V+ IM pigs, whereas the cell-mediated immune response was detected earlier in the V+ ID group at 2 weeks postvaccination. In the BAL fluid, a very low mucosal immune response (humoral and cellular) was detected. Postchallenge, the vaccine efficacy was similar in inoculated animals with partial control of PRRSV viremia in V+ ID and V+ IM animals. In vaccinated sentinel pigs, vaccination drastically reduced PRRSV transmission with similar estimated transmission rates and latency durations for the V+ IM and V+ ID groups. Conclusions: Our results show that the tested MLV1 induced a faster cell-mediated immune response after ID immunization two weeks after vaccination but was equally efficacious after IM or ID immunization towards a challenge four weeks later. Considering the practical and welfare benefits of ID vaccination, these data further support the use of this route for PRRS MLVs. [ABSTRACT FROM AUTHOR]

Abstract Tuberculosis is chronic infectious disease caused by Mycobacterium tuberculosis (M.tb) that is prevalent worldwide. Several specific antigens, such as Antigen 85B (Ag85B) and 6 kDa early secretory antigenic target (ESAT-6) protein of M.tb , are listed as some of the candidate subunit vaccines against M.tb. ESAT-6, as a virulent factor and differential gene in M.tb , shows insufficient immunogenicity in animal model. In order to investigate the ways to improve the immunogenicity of ESAT-6, we immunized ESAT-6 by subcutaneous and intramuscular routes with different adjuvants. We found that ESAT-6 immunized alone did not induce significant humoral immunity in both immunization routes. However, subcutaneous immunization of ESAT-6 plus incomplete Freund's adjuvant can induce a significant humoral immune response, enhanced proliferation and elevated secretion of IFN-γ from splenocytes. Intramuscular immunization of ESAT-6 plus adjuvant aluminum salt or poly(I:C) did not enhance humoral and cellular immune responses. Therefore, it is concluded that immunization of ESAT-6 subcutaneously plus incomplete Freund's adjuvant induces stronger humoral and cellular immune responses, which can be considered of ESAT-6 as a subunit vaccine in further research against tuberculosis. Highlights • ESAT-6 plus adjuvant immunized subcutaneously induces strong humoral immunity. • ESAT-6 plus adjuvant immunized subcutaneously induces strong cellular immunity. • Subcutaneous immunization of ESAT-6 is considered better than intramuscular route. [ABSTRACT FROM AUTHOR]

Virus-like particles (VLPs), a kind of superior subunit vaccine, are assembled from the viral structural proteins with similar capsids to viruses. However, the efficiency of cell uptake is not satisfactory. We prepared flower-like mesoporous silica nanoparticles (SiNPs) with large pore channels and interior cavities to solve the problem. The highly loaded VLPs-SiNPs composites not only enhanced the stability of VLPs, but also delivered antigen to cells and improved the cellular uptake efficiency. Compared with naked VLPs, mice intramuscularly immunized with the VLPs-SiNPs composite induced higher specific antibodies, greater lymphocyte activation and higher level of cytokine secretion. Moreover, the VLPs-SiNPs composite as vaccine also promoted mucosal immune response through intranasal immune pathway. Therefore, the VLPs-SiNPs enable to induce strong cellular, humoral, and slight mucosal immune response through different immunization routes. These results are potentially useful for vaccine formulations and may provide further reference for vaccine design and delivery systems. Silica nanoparticles loaded with antigen virus-like-particles (VLPs) improved the cellular uptake of antigen, and even enhanced the thermostability and acid-resistance. The vaccine formulation was immunized to mice with different immune routes, intramuscular injection and intranasal immunization. Both immune routes promote immune response; however, the intramuscular injection shows better cellular immune response and humoral immune response. [Display omitted] • Flower-like mesoporous silicon nanoparticles (SiNPs) with large pore channels and interior cavities were prepared. • The highly loaded VLPs-SiNPs can enhance the resistance to acid and thermo. • The SiNPs help deliver antigen to cells and improve cellular uptake of VLPs. • The SiNPs also played a role of adjuvants which can stimulate organisms to enhance immune response through different immune routes. [ABSTRACT FROM AUTHOR]

Abstract: Microparticles and nanoparticles represent promising carriers for the in vivo delivery of peptides, proteins or deoxyribonucleic acid (DNA). In this study, new hydroxyethylstarch (HES) microparticles were obtained by interfacial cross-linking with terephtaloyl chloride. These microparticles exhibit the characteristics required to improve antigen release and presentation to antigen presentating cells compared to free antigens. The adjuvant activity of HES microparticles as vaccine carrier was investigated in mice using bovine serum albumin (BSA) as model antigen. We showed HES microparticles were phagocyted by peritoneal mononuclear cells. The immunization with BSA-microparticles induced antibody synthesis that was predominantly immunoglobulin G1 (IgG1). Aluminium hydroxide remained more efficient to induce IgG synthesis. The analysis of the cytokine profile from spleen cells revealed that BSA-microparticles induced the secretion of both interferon-γ (IFN-γ) and interleukin-4 (IL-4). However, the immune responses induced by BSA-microparticles were qualitatively and quantitatively affected by the route of injection. Taken together, these results demonstrate that HES microparticles induce a mixed T helper 1/T helper 2 response against BSA and may be a suitable delivery and presentation system in the field of vaccine development. [Copyright &y& Elsevier]

We investigated the antibody (Ab) and cytotoxic T lymphocyte (CTL) responses to gene gun (GG)-mediated DNA immunization via the intramuscular (i.m.) and intradermal (i.d.) routes. BALB/c mice were immunized five times at weekly intervals with plasmid DNA encoding enhanced green fluorescent protein (EGFP). EGFP production was rapidly detected in the target tissues after injection via either delivery route. There were significant differences in the magnitude and duration of the Ab and CTL responses according to the route employed. Intradermal injection elicited higher Ab and CTL responses to EGFP than i.m. injection 1 week after the last immunization. However, both immune responses were reduced rapidly 5 weeks after the last immunization via i.d. injection. In contrast, in mice injected via the i.m. routes, Ab and CTL responses 5 weeks after the last immunization remained at levels similar to those detected after 1 week. All mice generated a predominantly IgG1 Ab response via either route. These findings suggest that a combination of these two routes of DNA immunization would provide optimal conditions for induction of a broad immune response, and this information is expected to be very important for future applications of DNA vaccination. [Copyright &y& Elsevier]