Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

Bissati, Kamal El; Chentoufi, Aziz Alami; Krishack, Paulette A.; Zhou, Ying; Woods, Stuart; Dubey, J. P.; Vang, Lo; Lykins, Joseph; Broderick, Kate E.; Mui, Ernest; Suzuki, Yasuhiro; Sa, Qila; Bi, Stephanie; Cardona, Néstor; Verma, Shiv Kumar; Fraczek, Laura; Reardon, Catherine A.; Sidney, John; Alexander, Jeff; Sette, Alessandro; Vedvick, Tom; Fox, Chris; Guderian, Jeffrey A.; Reed, Steven G.; Roberts, Craig W.; McLeod, Rima

doi:10.1172/jci.insight.85955

Cited by 41 publications

(70 citation statements)

References 45 publications

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“…Although not much time has passed since the introduction of the first report about computational vaccine design, in the recent years, a lot of progress has been made in this regard. Subsequently, numerous vaccines were developed based on computational approaches that include efficient vaccine against Toxoplasma gondii [31], Rickettsia prowazekii [32], Streptococcus pneumoniae [33], Leishmania infantum [34], Chlamydia pneumoniae [35], Brucella abortus [36], Staphylococcus aureus [15], Escherichia coli [37], Vibrio cholera [38], Human immunodeficiency virus-1 [39], Hepatitis C virus [40] and many others. In many empirical studies, the efficacy of computationally designed vaccines is approved [34,39,41,42].…”

Section: Introductionmentioning

confidence: 99%

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach

Nosrati

Behbahani

Mohabatkar

2019

Journal of Biomedical Informatics

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A R T I C L E I N F O Keywords:Crimean-Congo hemorrhagic fever Computer-aided vaccine design Multi-epitope vaccine A B S T R A C T Crimean-Congo hemorrhagic fever (CCHF) is considered one of the major public health concerns with case fatality rates of up to 80%. Currently, there is no effective approved vaccine for CCHF. In this study, we used a computer-aided vaccine design approach to develop the first multi-epitope recombinant vaccine for CCHF. For this purpose, linear B-cell and T-cell binding epitopes from two structural glycoproteins of CCHF virus including Gc and Gn were predicted. The epitopes were further studied regarding their antigenicity, allergenicity, hydrophobicity, stability, toxicity and population coverage. A total number of seven epitopes including five T-cell and two B-cell epitopes were screened for the final vaccine construct. Final vaccine construct composed of 382 amino acid residues which were organized in four domains including linear B-cell, T-cell epitopes and cholera toxin B-subunit (CTxB) along with heat labile enterotoxin IIc B subunit (LT-IIc) as adjuvants. All the segments were joined using appropriate linkers. The physicochemical properties as well as the presence of IFN-γ inducing epitopes in the proposed vaccine, was also checked to determining the vaccine stability, solubility and its ability to induce cell-mediated immune responses. The 3D structure of proposed vaccine was subjected to the prediction of computational B-cell epitopes and molecular docking studies with MHC-I and II molecules. Furthermore, molecular dynamics stimulations were performed to study the vaccine-MHCs complexes stability during stimulation time. The results suggest that our proposed vaccine was stable, well soluble in water and potentially antigenic. Results also demonstrated that the vaccine can induce both humoral and cell-mediated immune responses and could serve as a promising anti-CCHF vaccine candidate.

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Section: Introductionmentioning

confidence: 99%

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach

Nosrati

Behbahani

Mohabatkar

2019

Journal of Biomedical Informatics

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“…Therefore, it is recommended that a vaccine which can trigger the balance responses between Th1 and Th2 is highly favourable against schistosome infection. Alternative approach such as the application of multi‐valent vaccines (ie combination of several antigens as well as a mixture of immunogenic epitopes with suitable adjuvants) could be a potential strategy to improve protective efficacy against the parasite infection …”

Section: Discussionmentioning

confidence: 99%

Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni

Leow

Willis

Chuah

et al. 2020

Parasite Immunology

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Aims Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long‐term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model. Methods and results Bioinformatics analysis showed that there were three potential linear B‐cell epitopes and four conformational B‐cell epitopes predicted from annexin B30, respectively. Full‐length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected. Conclusion Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.

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“…A promising alternative delivery system for subunitbased vaccines has been developed recently [134] and used with vaccine candidates against several infectious diseases such as HIV [142], toxoplasma [143][144][145], SARS [146], influenza [147] and/or malaria [148][149][150]. The technique is known as Self-Assembling Protein Nanoparticles (SAPNs) and involves the expression of a peptide/ protein containing a target antigen covalently linked to an adjuvant sequence (flagellin-derived) and, in some cases, a universal epitope such as the Pan-DR T-helper epitope (PADRE) sequence.…”

Section: Future Directionsmentioning

confidence: 99%

Plasmodium falciparum pre-erythrocytic stage vaccine development

Molina-Franky

Cuy-Chaparro

Camargo

et al. 2020

Malar J

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Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.

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Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

Cited by 41 publications

References 45 publications

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach

Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni

Plasmodium falciparum pre-erythrocytic stage vaccine development

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