scholarly journals Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice

Author(s):  
Santiago Uranga ◽  
Dessislava Marinova ◽  
Carlos Martin ◽  
Nacho Aguilo
2020 ◽  
pp. IAI.00585-20
Author(s):  
Yaguo Wang ◽  
Zihui Li ◽  
Shucai Wu ◽  
Joy Fleming ◽  
Chuanyou Li ◽  
...  

Lack of efficacious vaccines against Mycobacterium tuberculosis (MTB) infection is a limiting factor in the prevention and control of tuberculosis (TB), the leading cause of death from an infectious agent. Improvement or replacement of the BCG vaccine with one that reliably protects all age-groups is urgent. Concerns exist that antigens currently being evaluated are too homogeneous. To identify new protective antigens, we screened 1781 proteins from a high-throughput proteome-wide protein purification study for antigenic activity. Forty-nine antigens (34 previously unreported) induced antigen-specific IFN-γ release from peripheral blood mononuclear cells (PBMCs) derived from 4452 TB and suspected TB patients and 167 healthy donors. Three (Rv1485, Rv1705c and Rv1802) of the 20 antigens evaluated in a BALB/c mouse challenge model showed protective efficacy, reducing lung CFU counts by 66.2%, 75.8%, and 60%, respectively. Evaluation of IgG2a:IgG1 ratios and cytokine release indicated that Rv1485 and Rv1705c induce a protective Th1 immune response. Epitope analysis of PE/PPE protein Rv1705c, the strongest candidate, identified a dominant epitope in its extreme N-terminal domain accounting for 90% of its immune response. Systematic pre-clinical assessment of antigens Rv1485 and Rv1705c is warranted.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Molalegne Bitew ◽  
Chintu Ravishankar ◽  
Soumendu Chakravarti ◽  
Gaurav Kumar Sharma ◽  
Sukdeb Nandi

Recent invasion of multiple bluetongue virus serotypes (BTV) in different regions of the world necessitates urgent development of efficient vaccine that is directed against multiple BTV serotypes. In this experimental study, cell mediated immune response and protective efficacy of binary ethylenimine (BEI) inactivated Montanide™ ISA 206 adjuvanted pentavalent (BTV-1, 2, 10, 16 and 23) vaccine was evaluated in sheep and direct challenge with homologous BTV serotypes in their respective group. Significant (P<0.05) up-regulation of mRNA transcripts of IFN-α, IL-2, IL-6, IL-12, IFN-γ and TNF-α in PBMCs of vaccinated animals as compared to control (un-vaccinated) animals at certain time points was observed. On the other hand, there was a significant increase in mean ± SD percentage of CD8+ T cells after 7 days post challenge (DPC) but, the mean ± SD percentage of CD4+ T-cell population slightly declined at 7 DPC and enhanced after 14 DPC. Significant differences (P<0.05) of CD8+ and CD4+ T cells population was also observed between vaccinated and unvaccinated sheep. The vaccine also significantly (P<0.05) reduced BTV RNA load in PBMCs of vaccinated animals than unvaccinated animals following challenge. There were no significant difference (P>0.05) in cytokine induction, BTV RNA load and CD8+ and CD4+ cell count among BTV-1, 2, 10, 16 and 23 serotype challenges except significant increase in mean ± SD percentage of CD8+ in BTV-2 group. These findings put forwarded that binary ethylenimine inactivated montanide adjuvanted pentavalent bluetongue vaccine has stimulated cell mediated immune response and most importantly reduced the severity of BTV-1, 2, 10, 16 and 23 infections following challenge in respective group.


mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e00583-17 ◽  
Author(s):  
K. Ross Turbyfill ◽  
Kristen A. Clarkson ◽  
Anthony R. Vortherms ◽  
Edwin V. Oaks ◽  
Robert W. Kaminski

ABSTRACTThe native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange-purified product derived from the water extract of virulentShigellaspecies. The key component of InvaplexNATis a high-molecular-mass complex (HMMC) consisting of theShigellalipopolysaccharide (LPS) and the invasin proteins IpaB and IpaC. To improve product purity and immunogenicity, artificial Invaplex (InvaplexAR) was developed using recombinant IpaB and IpaC proteins and purifiedShigellaLPS to assemble an HMMC consisting of all three components. Characterization of InvaplexARby various methods demonstrated similar characteristics as the previously reported HMMC in InvaplexNAT. The well-defined InvaplexARvaccine consistently contained greater quantities of IpaB, IpaC, and LPS than InvaplexNAT. InvaplexARand InvaplexNATimmunogenicities were compared in mouse and guinea pig dose escalation studies. In both models, immunization induced antibody responses specific for InvaplexNATand LPS while InvaplexARinduced markedly higher anti-IpaB and -IpaC serum IgG and IgA endpoint titers. In the murine model, homologous protection was achieved with 10-fold less InvaplexARthan InvaplexNATand mice receiving InvaplexARlost significantly less weight than mice receiving the same amount of InvaplexNAT. Moreover, mice immunized with InvaplexARwere protected from challenge with both homologous and heterologousShigellaserotypes. Guinea pigs receiving approximately 5-fold less InvaplexARcompared to cohorts immunized with InvaplexNATwere protected from ocular challenge. Furthermore, adjuvanticity previously attributed to InvaplexNATwas retained with InvaplexAR. The second-generationShigellaInvaplex vaccine, InvaplexAR, offers significant advantages over InvaplexNATin reproducibility, flexible yet defined composition, immunogenicity, and protective efficacy.IMPORTANCEShigellaspecies are bacteria that cause severe diarrheal disease worldwide, primarily in young children. Treatment of shigellosis includes oral fluids and antibiotics, but the high burden of disease, increasing prevalence of antibiotic resistance, and long-term health consequences clearly warrant the development of an effective vaccine. OneShigellavaccine under development is termed the invasin complex or Invaplex and is designed to drive an immune response to specific antigens of the bacteria in an effort to protect an individual from infection. The work presented here describes the production and evaluation of a new generation of Invaplex. The improved vaccine stimulates the production of antibodies in immunized mice and guinea pigs and protects these animals fromShigellainfection. The next step in the product’s development will be to test the safety and immune response induced in humans immunized with Invaplex.


2018 ◽  
Vol 258 ◽  
pp. 108-113 ◽  
Author(s):  
Shafiya Imtiaz Rafiqi ◽  
Rajat Garg ◽  
Reena K.K. ◽  
Hira Ram ◽  
Mithilesh Singh ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Seunga Choi ◽  
Han-Gyu Choi ◽  
Ki-Won Shin ◽  
Yong Woo Back ◽  
Hye-Soo Park ◽  
...  

The attenuated vaccineMycobacterium bovisBCG (Bacille Calmette Guerin) has limited protective efficacy against TB. The development of more effective TB vaccines has focused on the mycobacterial antigens that cause strong T helper 1 (Th1) responses. Mtb protein Rv3841 (bacterioferritin B; BfrB) is known to play a crucial role in the growth of Mtb. Nonetheless, it is unclear whether Rv3841 can induce protective immunity against Mtb. Here, we studied the action of Rv3841 in maturation of dendritic cells (DCs) and its engagement in the development of T-cell immunity. We found that Rv3841 functionally activated DCs by upregulating costimulatory molecules and increased secretion of proinflammatory cytokines. Activation of DCs by Rv3841 was mediated by Toll-like receptor 4 (TLR4), followed by triggering of mitogen-activated protein kinase and nuclear factor-κB signaling pathways. In addition, Rv3841-matured DCs effectively proliferated and polarized Th1 immune response of naïve CD4+and CD8+T-cells. Moreover, Rv3841 specifically caused the expansion of CD4+CD44highCD62LlowT-cells from Mtb-infected mice; besides, the T-cells activated by Rv3841-matured DCs inhibited intracellular mycobacterial growth. Our data suggest that Rv3841 induces DC maturation and protective immune responses, a finding that may provide candidate of effective TB vaccines.


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