scholarly journals 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 ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  

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.

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 852
Author(s):  
Khalid A. Alluhaybi ◽  
Rahaf H. Alharbi ◽  
Rowa Y. Alhabbab ◽  
Najwa D. Aljehani ◽  
Sawsan S. Alamri ◽  
...  

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.


1988 ◽  
pp. 185-196
Author(s):  
Anne Durandy ◽  
Alain Fischer ◽  
Edouard Drouhet ◽  
Claude Griscelli

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 724
Author(s):  
Justyna Gatkowska ◽  
Katarzyna Dzitko ◽  
Bartłomiej Tomasz Ferra ◽  
Lucyna Holec-Gąsior ◽  
Malwina Kawka ◽  
...  

Toxoplasmosis, one of the most common parasitoses worldwide, is potentially dangerous for individuals with a weakened immune system, but specific immunoprophylaxis intended for humans is still lacking. Thus, efforts have been made to create an efficient universal vaccine for both animals and humans to overcome the shortcomings of currently used treatment methods and protect all hosts against toxoplasmosis. The current work represents a relatively new approach to vaccine development based on recombinant chimeric Toxoplasma gondii antigens. In the present research, three tetravalent chimeric proteins containing different portions of the parasite’s AMA1 antigen—AMA1domainI-SAG2-GRA1-ROP1L (ANSGR), AMA1domainsII,III-SAG2-GRA1-ROP1L (ACSGR) and AMA1fullprotein-SAG2-GRA1-ROP1L (AFSGR)—were tested for their immunogenic and immunoprotective capacities. All tested proteins were immunogenic, as evidenced by the triggering of specific humoral and cellular immune responses in vaccinated C3H/HeOuJ mice, defined by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and synthesis of key Th1/Th2 cytokines by Toxoplasma lysate antigen-stimulated splenocytes in vitro. Although all tested preparations provided partial protection against chronic toxoplasmosis in immunized and T. gondii-challenged mice, the intensity of the generated immunoprotection depended on the fragment of the AMA1 antigen incorporated into the chimeric antigen’s structure.


1999 ◽  
Vol 67 (11) ◽  
pp. 5567-5572 ◽  
Author(s):  
Félix Romain ◽  
Cynthia Horn ◽  
Pascale Pescher ◽  
Abdelkader Namane ◽  
Michel Riviere ◽  
...  

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1384
Author(s):  
Haibo Feng ◽  
Jie Yang ◽  
Hui Zhi ◽  
Xin Hu ◽  
Yan Yang ◽  
...  

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.


2011 ◽  
Vol 19 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Bei Li ◽  
Chunhong Du ◽  
Lei Zhou ◽  
Yujing Bi ◽  
Xiaoyi Wang ◽  
...  

ABSTRACTPlague is one of the most dangerous diseases and is caused byYersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n= 65) recovered fromY. pestisinfection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r= 0.821;P< 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-γ), stimulated by F1 and LcrV, respectively,in vitroto the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines againstY. pestisinfection and the development of new target-based diagnostics.


2006 ◽  
Vol 55 (12) ◽  
pp. 1735-1740 ◽  
Author(s):  
Rachael C. Rigden ◽  
Dakshina M. Jandhyala ◽  
Chris Dupont ◽  
Dianna Crosbie-Caird ◽  
Nicolas Lopez-Villalobos ◽  
...  

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.


2020 ◽  
Author(s):  
naorem nihesh ◽  
Saikat Manna ◽  
Bradley Studnitzer ◽  
Jingjing Shen ◽  
Aaron Esser-Kahn

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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