Immunoprotection of FliBc chimeric fiber2 fusion proteins targeting dendritic cells against Fowl adenovirus serotype 4 infection
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Hepatitis-hydropericardium syndrome (HHS) is a highly fatal disease in chickens caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4), which has severe economic consequences. The fiber2 protein exhibits excellent potential as a candidate for a subunit vaccination against FAdV-4. Despite having a high safety profile, subunit vaccines have low immunogenicity due to their lack of infectivity, which leads to low levels of immune response. As a vaccine adjuvant, Salmonella flagellin possesses the potential to augment the immunological response to vaccinations. Additionally, a crucial strategy for enhancing vaccine efficacy is efficient presentation of immune antigens to dendritic cells (DC) for targeted vaccination. In this study, we designed FAdV-4-fiber2 protein and a recombinant protein called FliBc-fiber2-SP which based on FAdV-4-fiber2 protein, was generated using the gene sequence FliBc, which retains only the conserved sequence at the amino and carboxyl termini of the flagellin B subunit, and a short peptide SPHLHTSSPWER (SP), which targets chicken bone marrow-derived DC. They were separately administered via intramuscular injection to 14-day-old specific pathogen-free (SPF) chickens, and their immunogenicity was compared. At 21 days post vaccination (dpv), it was found that the FliBc-fiber2-SP recombinant protein elicited significantly higher levels of IgG antibodies and conferred a vaccine protection rate of up to 100% compared to its counterpart fiber2 protein. These results suggest that the DC-targeted peptide fusion strategy for flagellin chimeric antigen construction can effectively enhance the immune protective efficacy of antigen proteins.Keywords:
Flagellin
Direct immunogenicity comparison of adjuvants from various sources and with different mechanisms of action for inactivated influenza vaccines.Groups of mice were immunized intramuscularly twice with an inactivated whole-virion influenza vaccine based on A/California/07/2009 X-179A (H1N1) strain. The following adjuvants were added to the vaccine (10 in total): aluminium hydroxide, oligonucleotide CpG, complete Freund's adjuvant, poly(lactide-coglycolide) microparticles, monophosphoryl lipid A and polyoxidonium, as well as 2 adjuvants based on characterized chitosan substances with different physical/chemical properties and 2 experimental complex formulations (a multi-component adjuvant and an oil-in-water emulsion based on squalene and tocopherol). Immuogenicity was determined by HAI and MN (MDCK) sera antibodies.Different adjuvants increased immunogenicity of the vaccine against the homologous strain in varying patterns. Experimental complex formulations were the most immunogenic (antibody titer increase reached 48 - 96 times compared with unadjuvanted vaccines). Chitosan based adjuvants showed high immunogenicity. Not all the adjuvants significantly increased immunogenicity, and in some cases even an immunogenicity decrease was noted with the addition of certain adjuvants.Research and development of chitosan based adjuvants with characterization and standardization issues addressed, as well as complex adjuvants, both multi-component and emulsion based, are the most promising approaches that could lead to next generation vaccines against influenza and other human and animal infectious diseases.
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Chitosan-based adjuvants combine effectiveness, safety and economic feasibility and thus are quite promising for enhancement of influenza control via vaccination, however, problems of characterization and reproducibility remain unresolved; data on relations between physical-chemical characteristics (PCC) of the polymer and immunogenicity of chitosan-based adjuvants, as well as comparative evaluation with other adjuvants are needed. Groups of mice were immunized intramuscularly with inactivated influenza vaccines based on A/California/07/2009 (H1N1) strain with characterized adjuvants based on chitosan with varying PCC (molecular mass 700 and 10 kDa, deacetylation degree 85%; HMC and LMC, respectively) and its derivative (succinylated chitosan (SC)). Experimental formulations were also studied: an «oil-in-water» emulsion (ME) and a multi-component adjuvant (MS). Different adjuvants increased immunogenicity of the inactivated influenza vaccines by hemagglutinin inhibiting sera antibodies in varying patterns. HMC was more immunogenic than LMC, whereas SC even reduced immunogenicity of the vaccine. HMC was comparable to MS by immunogenicity, and LMC - to ME. PCC of chitosan and its derivatives play an important role in immunogenicity of the respective adjuvants, and perspective and characterized chitosan-based adjuvants are comparable or even more immunogenic than adjuvants from other groups.
Inactivated vaccine
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Objective To express BPI 23 Fcγ1 anti bacteria recombinant fusion protein. Methods BPI 23 and Fcγ1 genes were isolated by RT PCR from HL 60 and normal human leukocytes and inserted into expression vector pBV and the fusion protein expressed in E. coli DH5α in a temperature induced manner. Results The expressed BPI 23 Fcγ1 fusion protein constituted 20%～30% of total bacterial protein. The renatured BPI 23 Fcγ1 recombinant protein showed biological activities of anti bacteria and was able to form conjugate with protein A. Conclusion pBV BPI 600 Fcγ1 700 recombinant expression vector was successfully constructed, and BPI 23 Fcγ1 recombinant protein with anti bacteria activities was expressed in E. coli .
Protein A/G
Myc-tag
Target protein
Protein G
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Bacterial flagellin, as a pathogen-associated molecular pattern (PAMP), can activate both innate and adaptive immunity. Its unique structural characteristics endow an effective and flexible adjuvant activity, which allow the design of different types of vaccine strategies to prevent various diseases. This review will discuss recent progress in the mechanism of action of flagellin and its prospects for use as a vaccine adjuvant.Herein we summarize various types of information related to flagellin adjuvants from PubMed, including structures, signaling pathways, natural immunity, and extensive applications in vaccines, and it discusses the immunogenicity, safety, and efficacy of flagellin-adjuvanted vaccines in clinical trials.It is widely accepted that as an adjuvant, flagellin can induce an enhanced antigen-specific immune response. Flagellin adjuvants will allow more effective flagellin-based vaccines to enter clinical trials. Furthermore, vaccine formulations containing PAMPs are crucial to exert the maximum potential of vaccine antigens. Therefore, combinations of flagellin-adjuvanted vaccines with other adjuvants that act in a synergistic manner, particularly TLR ligands, represent a promising method for tailoring targeted vaccines to meet specific requirements.
Flagellin
TLR5
Vaccine adjuvant
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We sincerely appreciate Dr. Pandey’s interest in our review on flagellin and its adjuvant property. With regard to his comments, it is important to note that we were referring to clinical trials that assess the adjuvant property of flagellin and not necessarily its immunogenic potential. We agree
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Combined DNA vaccine encoding Ag85B, MPT64 and MPT83 of Mycobacterium tuberculosis were formulated into DDA and MPL to immunize mice and then the immunogenicity and protective efficacy of each group were evaluated. The DDA and MPL groups induced a much more enhanced Th1-type cellular response indicated by the higher levels of IFN-γ compared with that without any adjuvant. In DDA group, antigens specific IFN-γ for Ag85B, MPT64, MPT83 are (265.37±79.2) U/ml,(185.31±58.3) U/ml,(108.13±54.4) U/ml respectively which are 16 U/ml,45 U/ml,2 U/ml higher than that of the non-adjuvant group. The bacterial CFU in lungs and spleens of the DDA group was reduced 1/5 and 1/4 respectively relative to the same combined vaccine with MPL and without adjubvants. The pathological lungs slices of adjuvant groups gave consistent result that showed less damage than non-adjuvant group due to influx of epithelioid macrophages and less neutrophils. In conclusion, DDA is more efficacious than MPL as adjuvants to enhance immune efficacy of combined DNA vaccine in mice.
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Pneumolysin
Alum
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Aim. Evaluate specific immunogenic activity of a prototype vaccine against hepatitis E (HE). Materials and methods. Non-linear mice, male (n=170), were immunized once intraperitoneally by a prototype vaccine against HE at 5,10 and 20 pg per animal. Anti-HEV IgG were determined by ELISA using species-specific conjugate at days 7,14,21 and 28 after immunization. Experimental samples of the vaccine preparation containing 20 pg of the antigen and compositions of adjuvants based on aluminium hydroxide and immune modulators polyoxidonium and glutoxim were administered to 250 mice split into 25 groups (10 animals per group) to optimize vaccine immuno-genicity. Anti-HEV were determined in mice sera samples at day 28 after the immunization, and mean immunization dose (Ш50) for each composition of the vaccine preparation was calculated. Results. Increase of immunogenicity for the same standard antigen dose (20 pg) for glutoxim adjuvant at 10 mg/ml in aluminium hydroxide solution (0,5 mg/ml) was 51.4%. A non-significant increase of immunogenicity was also observed for vaccine composition with polyoxidonium (1.0 mg/ml), however, it was statistically non-significant when compared with standard adjuvant (aluminium hydroxide at 0,5 mg/ml). Conclusion. The data obtained give evidence regarding high immunogenicity of the vaccine preparation against hepatitis E. Use of glutoxim immune modulator in the composition of the experimental vaccine against hepatitis E ensures highest immunogenicity.
Hepatitis B vaccine
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Summary Antibody production in the rat in response to the injection of Salmonella adelaide flagellin was considerably enhanced if the antigen were Injected In emulsion with Freund's complete adjuvant. Peak titres of antibody Were 1000‐fold higher than those obtained following the injection of antigen alone. However the minimal dose of flagellin. which would stimulate antibody production was found to be of the order of 10 ng. (10 −8 g.) regardless of whether it were injected in adjuvant or in aqueous solution. Simultaneous injection of flagellin and adjuvant into opposite sides of the body resulted in only a very moderate enhancement of the antibody response. Rats which had been given a ten‐week course of bi‐weekly injections of flagellin starting in the neonatal period, and which were virtually unresponsive to subsequent challenge with flagellin, broke tolerance and produced high titres of antibody when challenged with the same dose of flagellin in adjuvant. These results have been interpreted in terms of the ability of antigen injected in Freund's complete adjuvant to be retained in the body for a considerable period of time where it remains available to stimulate both cells which “escape” the state of immune unresponsiveness and newly recruited antigen‐ sensitive cells whose proliferation is accelerated by the presence of the adjuvant.
Flagellin
Antibody response
Freund's adjuvant
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Design of an effective and safe vaccine against pathogenic streptococci is still on the agenda, in spite of numerous attempts in this area undertaken by different laboratories. In order to improve immunogenicity of recombinant vaccine preparations, a selection of effective adjuvants is necessary. Previously, two recombinant GBS polypeptides P6 and ScaAB were found to be immunogenic, and their injection in separate preparations or mixed manner boosted production of specific and protective antibodies with high affinity. Four different adjuvants (Freund adjuvant, aluminum hydroxide, Bestim and Interleukine-1β) have been tested for immunization of mice with single polypeptides, or with their mixtures. As a result of vaccination, it was demonstrated that aluminum hydroxide was providing the most desirable immunological parameters of immune response among the adjuvants tested. A mixture of polypeptides containing aluminum hydroxide was found to produce specific antibodies with better opsonizing activity against group B streptococci. (Med. Immunol., 2008, vol. 10, N 2-3, pp 215-222) .
Streptococcus Pyogenes
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