A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity

AbstractThe 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

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Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients

Journal of Clinical Investigation ◽

10.1172/jci11752 ◽

2001 ◽

Vol 107 (4) ◽

pp. 477-484 ◽

Cited By ~ 233

Author(s):

Keith L. Knutson ◽

Kathy Schiffman ◽

Mary L. Disis

Keyword(s):

T Cell ◽

Cancer Patients ◽

Peptide Vaccine ◽

Cd8 T Cell ◽

T Cell Immunity ◽

Cell Immunity ◽

Her 2 ◽

Helper Peptide

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Clinical efficacy and immunogenicity of the optimized cryptic peptide TERT572Y vaccine (Vx-001) in patients with advanced non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17069 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17069-17069

Author(s):

K. Kosmatopoulos ◽

E. Bolonaki ◽

D. Aggouraki ◽

E. Nikoloudi ◽

P. Kanellou ◽

...

Keyword(s):

T Cell ◽

Clinical Efficacy ◽

Peptide Vaccine ◽

Stage Iv ◽

Skin Toxicity ◽

T Cell Immunity ◽

Stage Iiib ◽

Cell Immunity ◽

Cryptic Peptide

17069 Background: BTERT572Y, an optimized cryptic peptide homologous to TERT induces efficient antitumoral T cell cytotoxic immunity but not autoreactivity in vivo in HLA-A*0201 transgenic mice and healthy blood donors and prostate cancer patients (J. Clin. Invest., 2004, 113,425). Moreover, it was well tolerated and effective in eliciting specific T cell immunity in patients (pts) with advanced malignancies (ASCO 2005, abstr 2579). Methods: We evaluated its clinical efficacy, safety and immunogenicity in 13 HLA-A*0201 pts with advanced, stage IIIb (7 pts) and stage IV (6 pts), NSCLC. Three pts were in stable (SD) and ten pts in progressive (PD) disease following prior therapy. The vaccination protocol consisted of two subcutaneous injections of optimized TERT572Y peptide followed by four injections of native TERT572 peptide. Both peptides were emulsified in Montanide ISA51. Results: Eight pts completed the entire vaccination program, 4 discontinued due to PD and 1 is ongoing. The median follow up is 6.5 months (range 2.0–29.9). Three of 10 (30%) pts with prior PD developed SD for 6+, 7+ and 9 months. Overall clinical response was SD in 6 and PD in 7 pts. Median TTP was 8.1 months (range 3.7–9.1) for stage IIIb and 2.3 (range 2–6.9) for stage IV pts. Minimal grade I/II primarily skin toxicity was observed. ELISPot-detected TERT572 specific CD8+ cells were demonstrated in all 7 pts tested. Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. The disease stabilization observed in 30% of pts with previously progressive disease is very encouraging and deserves further evaluation. [Table: see text]

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Potent Anti-Delta Effect By a Booster Third-Dose of UB-612, a Precision-Designed SARS-CoV-2 Multitope Protein-Peptide Vaccine

10.21203/rs.3.rs-944205/v1 ◽

2021 ◽

Author(s):

Chang Yi wang ◽

Kao-Pin Hwang ◽

Hui-Kai Kuo ◽

James Peng ◽

Daphne Shen ◽

...

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Phase 1 ◽

Peptide Vaccine ◽

Peptide Pool ◽

T Cell Immunity ◽

Breakthrough Infection ◽

Clinical Phase ◽

Cell Immunity ◽

Waning Immunity

Abstract SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

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