Engineered protein destabilization reverses intrinsic immune evasion for candidate vaccine pan-strain KSHV and SARS-CoV-2 antigens
Wan, L.; Xie, B.; Shuda, M.; Delgoffe, G. M.; Chang, Y.; Moore, P. S.
Show abstract
Both Kaposi sarcoma herpesvirus LANA and SARS coronavirus 2 RdRp/nsp12 are highly conserved replication proteins that evade immune processing. By deleting the LANA central repeat 1 domain (LANA{Delta}CR1) or by dividing RdRp into two separated fragments (RdRpFrag) to maximize nascent protein mis-folding, cis peptide presentation was increased. Native LANA or RdRp SIINFEKL fusion proteins expressed in MC38 cancer cells were not recognized by activated OT-1 CD8+ cells against SIINFEKL but cytotoxic recognition was restored by expression of the corresponding modified proteins. Immunocompetent syngeneic mice injected with LANA- or RdRp-SIINFEKL MC38 cells developed rapidly-growing tumors with short median survival times. Mice injected with LANA{Delta}CR1- or RdRpFrag-SIINFEKL had partial tumor regression, slower tumor growth, longer median survival, as well as increased effector-specific tumor-infiltrating lymphocytes. These mice developed robust T cell responses lasting at least 90 days post-injection that recognized native viral protein epitopes. Engineered vaccine candidate antigens can unmask virus-specific CTL responses that are typically suppressed during native viral infection.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The spontaneous neoantigen-specific CD4+ T cell response to a growing tumor is functionally and phenotypically diverse. 96%
- Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma 96%
- Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion 96%
Similar papers in this journal
- Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques 96%
- Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination 96%
- Memory B cell Development in Response to mRNA SARS-CoV-2 and Nanoparticle Immunization in Mice 96%
Similar papers in this journal
- Naive and in vitro-activated primary mouse CD8+ T cells retain in vivo immune responsiveness after electroporation-based CRISPR/Cas9 genetic engineering 96%
- Combination of a Sindbis-SARS-CoV-2 spike vaccine and αOX40 antibody elicits protective immunity against SARS-CoV-2 induced disease and potentiates long-term SARS-CoV-2-specific humoral and T-cell immunity 95%
- A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta 95%
Similar papers in this journal
- Cellular selectivity of STING stimulation determines priming of tumor-specific T cell responses 95%
- Affinity-engineered human antibodies detect celiac disease gluten pMHC complexes and inhibit T-cell activation 94%
- Three functionally distinct classes of cGAS proteins in nature revealed by self-DNA-induced interferon responses 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.