Modification to the Capsid of the Adenovirus Vector That Enhances Dendritic Cell Infection and Transgene-Specific Cellular Immune Responses

ABSTRACT Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing β-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the β-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing β-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to β-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-β-galactosidase antibody levels following vector administration. However, cellular responses to β-galactosidase were significantly enhanced, with the frequency of CD4+ as well as the CD8+ β-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing β-galactosidase: BALB/c mice implanted with the CT26 syngeneic β-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif to the Ad fiber knob increases the infectibility of DC and leads to enhanced cellular immune responses to the Ad-transferred transgene, suggesting that the RGD capsid modification may be useful in developing Ad-based vaccines.

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A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽

10.3390/vaccines9121408 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1408

Author(s):

Qiao Li ◽

Zhihua Liu ◽

Yi Liu ◽

Chen Liang ◽

Jiayi Shu ◽

...

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Inbred Mouse ◽

Effective Vaccine ◽

Mouse Strains ◽

Cellular Immune Responses ◽

Recombinant Hbsag ◽

Cellular Immune

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.

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Mannan Antigen of Candida Albicans and Cellular Immune Responses in Vitro and in Vivo

Fungal Antigens ◽

10.1007/978-1-4613-0773-0_13 ◽

1988 ◽

pp. 185-196

Author(s):

Anne Durandy ◽

Alain Fischer ◽

Edouard Drouhet ◽

Claude Griscelli

Keyword(s):

Candida Albicans ◽

Immune Responses ◽

Cellular Immune Responses ◽

Cellular Immune

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Deglycosylation of the 45/47-Kilodalton Antigen Complex of Mycobacterium tuberculosis Decreases Its Capacity To Elicit In Vivo or In Vitro Cellular Immune Responses

Infection and Immunity ◽

10.1128/iai.67.11.5567-5572.1999 ◽

1999 ◽

Vol 67 (11) ◽

pp. 5567-5572 ◽

Cited By ~ 66

Author(s):

Félix Romain ◽

Cynthia Horn ◽

Pascale Pescher ◽

Abdelkader Namane ◽

Michel Riviere ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

T Lymphocytes ◽

Immune Responses ◽

Delayed Type Hypersensitivity ◽

Cellular Immune Responses ◽

Antigen Complex ◽

Cellular Immune ◽

Living Bacteria

ABSTRACT A protection against a challenge with Mycobacterium tuberculosis is induced by previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). The 45/47-kDa antigen complex (Apa) present in culture filtrates of BCG of M. tuberculosis has been identified and isolated based on its ability to interact mainly with T lymphocytes and/or antibodies induced by immunization with living bacteria. The protein is glycosylated. A large batch of Apa was purified from M. tuberculosis culture filtrate to determine the extent of glycosylation and its role on the expression of the immune responses. Mass spectrometry revealed a spectrum of glycosylated molecules, with the majority of species bearing six, seven, or eight mannose residues (22, 24, and 17%, respectively), while others three, four, or five mannoses (5, 9, and 14%, respectively). Molecules with one, two, or nine mannoses were rare (1.5, 3, and 3%, respectively), as were unglycosylated species (in the range of 1%). To eliminate the mannose residues linked to the protein, the glycosylated Apa molecules were chemically or enzymatically treated. The deglycosylated antigen was 10-fold less active than native molecules in eliciting delayed-type hypersensitivity reactions in guinea pigs immunized with BCG. It was 30-fold less active than native molecules when assayed in vitro for its capacity to stimulate T lymphocytes primed in vivo. The presence of the mannose residues on the Apa protein was essential for the antigenicity of the molecules in T-cell-dependent immune responses in vitro and in vivo.

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Eucommia ulmoides Leaf Polysaccharide in Conjugation with Ovalbumin Act as Delivery System Can Improve Immune Response

Pharmaceutics ◽

10.3390/pharmaceutics13091384 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1384

Author(s):

Haibo Feng ◽

Jie Yang ◽

Hui Zhi ◽

Xin Hu ◽

Yan Yang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Delivery System ◽

Physicochemical Characteristics ◽

Cellular Immune Responses ◽

Ethylcarbodiimide Hydrochloride ◽

Ifn Γ ◽

Cellular Immune

In this investigation, to maximize the desired immunoenhancement effects of PsEUL and stimulate an efficient humoral and cellular immune response against an antigen, PsEUL and the model antigen ovalbumin (OVA) were coupled using the N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) reaction to yield a novel delivery system (PsEUL-OVA). The physicochemical characteristics and immune regulation effects of this new system were investigated. We found the yield of this EDC method to be 46.25%. In vitro, PsEUL-OVA (200 μg mL−1) could enhance macrophage proliferation and increase their phagocytic efficiency. In vivo, PsEUL-OVA could significantly increase the levels of OVA-specific antibody (IgG, IgG1, IgG2a, and IgG2b) titers and cytokine (IL-2, IL-4, IL-6, IFN-γ) levels. Additionally, it could activate T lymphocytes and facilitate the maturation of dendritic cells (DCs). These findings collectively suggested that PsEUL-OVA induced humoral and cellular immune responses by promoting the phagocytic activity of macrophages and DCs. Taken together, these results revealed that PsEUL-OVA had the potential to improve immune responses and provide a promising theoretical basis for the design of a novel delivery system.

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Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines

Vaccine ◽

10.1016/0264-410x(94)90290-9 ◽

1994 ◽

Vol 12 (9) ◽

pp. 812-818 ◽

Cited By ~ 44

Author(s):

G LEROUXROELS ◽

E VANHECKE ◽

W MICHIELSEN ◽

P VOET ◽

P HAUSER ◽

...

Keyword(s):

Hepatitis B ◽

Immune Responses ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Cellular Immune Responses ◽

Cellular Immune

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Humoral and cellular immune responses in sheep immunized with a 22 kilodalton exported protein of Mycobacterium avium subspecies paratuberculosis

Journal of Medical Microbiology ◽

10.1099/jmm.0.46785-0 ◽

2006 ◽

Vol 55 (12) ◽

pp. 1735-1740 ◽

Cited By ~ 14

Author(s):

Rachael C. Rigden ◽

Dakshina M. Jandhyala ◽

Chris Dupont ◽

Dianna Crosbie-Caird ◽

Nicolas Lopez-Villalobos ◽

...

Keyword(s):

Immune Responses ◽

Mycobacterium Avium ◽

Mycobacterium Avium Subspecies Paratuberculosis ◽

Specific Antibodies ◽

Antibody Recognition ◽

Cellular Immune Responses ◽

Exported Protein ◽

Cellular Immune

An immunogenic 22 kilodalton exported Mycobacterium avium subspecies paratuberculosis (MAP) lipoprotein (P22) was previously identified, and found to belong to the LppX/LprAFG family of mycobacterial lipoproteins. N-terminal polyhistidine-tagged P22 was produced and purified from Escherichia coli. Antibody recognition of P22, and interferon-gamma (IFN-γ) responses in vitro using blood from a sheep vaccinated with Neoparasec, confirmed its immunogenicity. To evaluate the immunogenicity of P22 in vivo, five sheep were immunized with a single dose containing 0.8 mg recombinant P22 protein in adjuvant. Blood was collected at 4, 13 and 29 weeks post-immunization (p.i.) and tested for anti-P22 antibodies and P22-specific IFN-γ production. P22-specific antibodies were detected by Western blot analysis in all five Neoparasec-immunized sheep at the three time points. Three out of five P22-immunized sheep produced P22-specific antibodies for up to 13 weeks p.i., and two gave a response at 29 weeks p.i. Recombinant P22 was able to stimulate significant IFN-γ production in blood of P22-immunized sheep at 13 and 29 weeks p.i. Recombinant P22 also elicited an IFN-γ response in blood of sheep immunized with Neoparasec.

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Modulation of cellular-immune responses in vivo and in vitro by histamine receptor-bearing lymphocytes.

Journal of Clinical Investigation ◽

10.1172/jci108347 ◽

1976 ◽

Vol 57 (4) ◽

pp. 1051-1058 ◽

Cited By ~ 225

Author(s):

R E Rocklin

Keyword(s):

Immune Responses ◽

Histamine Receptor ◽

Cellular Immune Responses ◽

Cellular Immune

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A Pathogen Mimetic Molecule Induces Highly Amplified Synergistic Immune Activation to Vaccination via Activation of Multiple Signaling Pathways

10.26434/chemrxiv.13105316.v1 ◽

2020 ◽

Author(s):

naorem nihesh ◽

Saikat Manna ◽

Bradley Studnitzer ◽

Jingjing Shen ◽

Aaron Esser-Kahn

Keyword(s):

Immune Response ◽

Immune Responses ◽

Nlrp3 Inflammasome ◽

Innate Immune ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Multiple Signaling ◽

Stimulation Pattern

We developed a small-molecule trimeric PRR agonist-based adjuvant inspired by the stimulation pattern of a pathogen. This molecule generated by covalently linking TLR2/6 agonist, NOD2 agonist, and NLRP3 inflammasome activator, stimulates multiple subfamilies of PRRs in a spatially defined manner resulting in an amplified innate immune response <i>in vitro.</i> Moreover, it elicits both stronger humoral and cellular immune responses <i>in vivo</i>.

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