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heterologous immunity

Chengchao Ding, Junfei Ma, Qingli Dong, Qing Liu
Live bacteria, including attenuated bacteria and probiotics, can be engineered to deliver target antigen to excite the host immune system. The preponderance of these live bacterial vaccine vectors is that they can stimulate durable humoral and cellular immunity. Moreover, delivery strategies of heterologous antigen in live bacterial promote the applications of new vaccine development. Genetic technologies are evolving, which potentiate the developing of heterologous antigen delivery systems, including bacterial surface display system, bacterial secretion system and balanced lethal vector system...
March 14, 2018: Immunology Letters
Mohammad Reza Asadi Karam, Ali Mohammad Shirzad, Mehri Habibi, Saeid Bouzari
Complicated urinary tract infections (UTIs) caused by Proteus mirabilis are among the most common disorders. An effective vaccine could reduce the prevalence of such infections and antibiotic resistance in society. In the present study, the immunogenicity and protective efficacy of different combinations of the MrpH adhesion and flagellin (FliC) of P. mirabilis was evaluated in a prime-boost strategy of vaccination. Applying the FliC as an adjuvant resulted in the stimulation of mixed Th1- and Th2-immune responses against the truncated form of MrpH with a shift toward Th1...
March 14, 2018: International Immunopharmacology
D Lapuente, M Storcksdieck Genannt Bonsmann, A Maaske, V Stab, V Heinecke, K Watzstedt, R Heß, A M Westendorf, W Bayer, C Ehrhardt, M Tenbusch
A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies...
March 15, 2018: Mucosal Immunology
John L M Law, Michael Logan, Jason Wong, Juthika Kundu, Darren Hockman, Amir Landi, Chao Chen, Kevin Crawford, Mark Wininger, Janelle Johnson, Catalina Mesa Prince, Elzbieta Dudek, Ninad Mehta, D Lorne Tyrrell, Michael Houghton
Current evidence supports a protective role for virus neutralizing antibodies in immunity against HCV infection. Many cross-neutralizing monoclonal antibodies have been identified. These antibodies have been shown to protect or clear infection in animal models. Previous clinical trials have shown a gpE1/gpE2 vaccine can induce antibodies that neutralize the in vitro infectivity of all the major HCVcc genotypes around the world. However, cross-neutralization appeared to favour certain genotypes with significant but lower neutralization against others...
March 14, 2018: Journal of Virology
Shelly Popowich, Ashish Gupta, Betty Chow-Lockerbie, Lisanework Ayalew, Neil Ambrose, Davor Ojkic, Thushari Gunawardana, Shanika Kurukulasuriya, Philip Willson, Suresh K Tikoo, Susantha Gomis
Historically, fowl adenovirus (FAdV) associated inclusion body hepatitis (IBH) was considered a secondary disease in broiler chickens associated with immunosuppression. However, we previously reported the occurrence of IBH as a primary disease in the broiler chicken industry in Canada as a result of infections with various FAdV serotypes. Therefore, the objectives of this study were to develop an immunization strategy in broiler breeders using live FAdV 11-1047 and FAdV8a-TR59 to confer homologous and heterologous protection in broiler progeny against IBH and to study the efficacy of natural exposure of naïve broiler breeders to a vaccine virus from live FAdV vaccinated birds as an immunization technique...
March 5, 2018: Research in Veterinary Science
Jamie Jennings-Gee, Sally Quataert, Tridib Ganguly, Ralph D'Agostino, Rajendar Deora, Purnima Dubey
The reemergence of pertussis or whooping cough in several countries highlights the need for better vaccines. Acellular pertussis vaccines (aPV) contain alum as the adjuvant and elicit Th2 biased immune responses that are less effective in protecting against infection than the reactogenic whole cell pertussis vaccines (wPV), which elicit primarily a Th1/Th17 response. An important goal for the field is to devise aPVs that will induce immune responses similar to wPV. We show that Bordetella Colonization Factor A (BcfA), an outer membrane protein from B...
March 12, 2018: Infection and Immunity
Jie Zhang, Wenming Zong, Wei Hong, Zhong-Tian Zhang, Yi Wang
Although CRISPR-Cas9/Cpf1 have been employed as powerful genome engineering tools, heterologous CRISPR-Cas9/Cpf1 are often difficult to introduce into bacteria and archaea due to their severe toxicity. Since most prokaryotes harbor native CRISPR-Cas systems, genome engineering can be achieved by harnessing these endogenous immune systems. Here, we report the exploitation of Type I-B CRISPR-Cas of Clostridium tyrobutyricum for genome engineering. In silico CRISPR array analysis and plasmid interference assay revealed that TCA or TCG at the 5'-end of the protospacer was the functional protospacer adjacent motif (PAM) for CRISPR targeting...
March 9, 2018: Metabolic Engineering
Iván Pastor-Fernández, Sungwon Kim, Karen Billington, Janene Bumstead, Virginia Marugán-Hernández, Tatiana Küster, David J P Ferguson, Lonneke Vervelde, Damer P Blake, Fiona M Tomley
Recently, the availability of protocols supporting genetic complementation of Eimeria has raised the prospect of generating transgenic parasite lines which can function as vaccine vectors, expressing and delivering heterologous proteins. Complementation with sequences encoding immunoprotective antigens from other Eimeria spp. offers an opportunity to reduce the complexity of species/strains in anticoccidial vaccines. Herein, we characterise and evaluate EtAMA1 and EtAMA2, two members of the apical membrane antigen (AMA) family of parasite surface proteins from Eimeria tenella...
March 7, 2018: International Journal for Parasitology
L Coughlan, S Sridhar, R Payne, M Edmans, A Milicic, N Venkatraman, B Lugonja, L Clifton, C Qi, P M Folegatti, A M Lawrie, R Roberts, H de Graaf, P Sukhtankar, S N Faust, D J M Lewis, T Lambe, Avs Hill, S C Gilbert
BACKGROUND: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1)...
February 15, 2018: EBioMedicine
Rose M Langsjoen, Sherry L Haller, Chad J Roy, Heather Vinet-Oliphant, Nicholas A Bergren, Jesse H Erasmus, Jill A Livengood, Tim D Powell, Scott C Weaver, Shannan L Rossi
Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported...
March 6, 2018: MBio
Dandan Wang, Jingcai Lu, Jinfei Yu, Hongjia Hou, Kees Leenhouts, Maarten L Van Roosmalen, Tiejun Gu, Chunlai Jiang, Wei Kong, Yongge Wu
BACKGROUND: Streptococcus pneumoniae is a major pathogen accounting for a large number of pneumococcal disease in worldwide. Due to the mucosal immune pathway induces both systemic and mucosal immune responses, the potential strategy to prevent pneumococcal disease may be to develop a mucosal vaccine. METHOD: In this study, we developed an intranasal pneumococcal protein vaccine based on a bacterium-like particle (BLP) delivery system. PspA is expressed and exposed on the surface of all pneumococcal strains, which confers the potential to induce immune responses to protect against pneumococcal infection...
March 2, 2018: Immunological Investigations
Kunitaka Yoshida, Mitsuhiro Iyori, Andrew M Blagborough, Ahmed M Salman, Pawan Dulal, Katarzyna A Sala, Daisuke S Yamamoto, Shahid M Khan, Chris J Janse, Sumi Biswas, Tatsuya Yoshii, Yenni Yusuf, Masaharu Tokoro, Adrian V S Hill, Shigeto Yoshida
With the increasing prevalence of artemisinin-resistant malaria parasites, a highly efficacious and durable vaccine for malaria is urgently required. We have developed an experimental virus-vectored vaccine platform based on an envelope-modified baculovirus dual-expression system (emBDES). Here, we show a conceptually new vaccine platform based on an adenovirus-prime/emBDES-boost heterologous immunization regimen expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). A human adenovirus 5-prime/emBDES-boost heterologous immunization regimen consistently achieved higher sterile protection against transgenic P...
March 1, 2018: Scientific Reports
Huafang Lai, Amber M Paul, Haiyan Sun, Junyun He, Ming Yang, Fengwei Bai, Qiang Chen
West Nile virus (WNV) has caused multiple global outbreaks with increased frequency of neuroinvasive disease in recent years. Despite many years of research, there are no licensed therapeutics or vaccines available for human use. One of the major impediments of vaccine development against WNV is the potential enhancement of infection by related flaviviruses in vaccinated subjects through the mechanism of antibody-dependent enhancement of infection (ADE). For instance, the recent finding of enhancement of Zika virus (ZIKV) infection by pre-exposure to WNV further complicates the development of WNV vaccines...
February 26, 2018: Vaccine
Congmin Liu, Xiaowen Dou, Lei Zhang, Weijun Kong, Liu Wu, Yaping Duan, Meihua Yang
In the present study, molecular modeling and principle component analysis (PCA) were used to select appropriate haptens for group detection of triazine herbicides. Four new structures together with three reported triazine derivatives were chosen for the screening of immunizing and coating haptens. A total of 31 triazines coupled with a 3D-QSAR methodology were employed to investigate the relationship between antigen-antibody recognition and molecular structures, the results of which revealed that the antibodies may recognize triazines from the side of molecules with the distinguishing atom and a steric volume matching with the spatial structure of antibodies...
July 5, 2018: Analytica Chimica Acta
P J Klasse, Thomas J Ketas, Christopher A Cottrell, Gabriel Ozorowski, Gargi Debnath, Diawoye Camara, Erik Francomano, Pavel Pugach, Rajesh P Ringe, Celia C LaBranche, Marit J van Gils, Christine A Bricault, Dan H Barouch, Shane Crotty, Guido Silvestri, Sudhir Kasturi, Bali Pulendran, Ian A Wilson, David C Montefiori, Rogier W Sanders, Andrew B Ward, John P Moore
The native-like, soluble SOSIP.664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species, of which the most studied are rabbits and rhesus macaques. The trimer induces autologous neutralizing antibodies (NAbs) consistently but at a wide range of titers and with incompletely determined specificities. A precise delineation of immunogenic neutralization epitopes on native-like trimers could help strategies to extend the NAb response to heterologous HIV-1 strains. One autologous NAb epitope on the BG505 Env trimer is known to involve residues lining a hole in the glycan shield that is blocked by adding a glycan at either residue 241 or 289...
February 23, 2018: PLoS Pathogens
Yu Zhou, Chao Zhang, Qingwei Liu, Sitang Gong, Lanlan Geng, Zhong Huang
Coxsackievirus A10 (CVA10) has emerged worldwide as one of the main pathogens of hand, foot, and mouth disease (HFMD) in recent years. However, there is currently no commercial vaccine available to prevent CVA10 infection. Here we report the development of a recombinant virus-like particle (VLP) based candidate vaccine for CVA10. Co-expression of the capsid protein precursor P1 and the protease 3CD of CVA10 in Pichia pastoris resulted in cleavage of P1 into three capsid subunit proteins VP0, VP1, and VP3. These three subunit proteins co-assembled into CVA10 VLPs, which were visualized as spherical particles with a diameter of ∼30 nm under electron microscope...
February 19, 2018: Antiviral Research
Carly M Bliss, Georgina Bowyer, Nicholas A Anagnostou, Tom Havelock, Claudia M Snudden, Huw Davies, Simone C de Cassan, Amy Grobbelaar, Alison M Lawrie, Navin Venkatraman, Ian D Poulton, Rachel Roberts, Pooja B Mange, Prateek Choudhary, Saul N Faust, Stefano Colloca, Sarah C Gilbert, Alfredo Nicosia, Adrian V S Hill, Katie J Ewer
Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors...
February 21, 2018: Scientific Reports
Gema Lorenzo, Elena López-Gil, Javier Ortego, Alejandro Brun
The aim of this work was to evaluate the immunogenicity and efficacy of DNA and MVA vaccines encoding the RVFV glycoproteins Gn and Gc in an ovine model of RVFV infection. Adult sheep of both sexes were challenged 12 weeks after the last immunization and clinical, virological, biochemical and immunological consequences, were analyzed. Strategies based on immunization with homologous DNA or heterologous DNA/MVA prime-boost were able to induce a rapid in vitro neutralizing antibody response as well as IFNγ production after in vitro virus specific re-stimulation...
February 21, 2018: Veterinary Research
Christopher W Pohlmeyer, Sarah B Laskey, Sarah E Beck, Daniel C Xu, Adam A Capoferri, Caroline C Garliss, Megan E May, Alison Livingston, Walt Lichmira, Richard D Moore, M Sue Leffell, Nicholas J Butler, Jennifer E Thorne, John A Flynn, Robert F Siliciano, Joel N Blankson
Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects...
2018: PloS One
Matthias Konrad, Christopher D Pull, Sina Metzler, Katharina Seif, Elisabeth Naderlinger, Anna V Grasse, Sylvia Cremer
Being cared for when sick is a benefit of sociality that can reduce disease and improve survival of group members. However, individuals providing care risk contracting infectious diseases themselves. If they contract a low pathogen dose, they may develop low-level infections that do not cause disease but still affect host immunity by either decreasing or increasing the host's vulnerability to subsequent infections. Caring for contagious individuals can thus significantly alter the future disease susceptibility of caregivers...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
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