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

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]

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

Nature ◽  
2021 ◽  
Author(s):  
Jonas S. Heitmann ◽  
Tatjana Bilich ◽  
Claudia Tandler ◽  
Annika Nelde ◽  
Yacine Maringer ◽  
...  
Keyword(s):  
T Cell ◽  
Peptide Vaccine ◽  
T Cell Immunity ◽  
Cell Immunity

scholarly journals An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design

2020 ◽  
Author(s):  
CV Herst ◽  
S Burkholz ◽  
J Sidney ◽  
A Sette ◽  
PE Harris ◽  
...  
Keyword(s):  
T Cell ◽  
Nucleocapsid Protein ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cell Vaccine ◽  
Amino Acid Peptide ◽  
T Cell Vaccine ◽  
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.

scholarly journals Long-term follow-up of SARS-CoV-2 convalescents reveals distinct magnitude of spike-specific immunity after viral re-exposure and vaccination

2021 ◽  
Author(s):  
Percy Knolle ◽  
Nina Körber ◽  
Alina Priller ◽  
Sarah Yazici ◽  
Tanja Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Specific Immunity ◽  
Cell Immunity

Abstract Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is controlled by the host´s immune response1-4, but longitudinal follow-up studies of virus-specific immunity to evaluate protection from re-infection are lacking. Here, we report the results from a prospective study that started during the first wave of the COVID-19 pandemic in spring 2020, where we identified 91 convalescents from mild SARS-CoV-2 infection among 4554 health care workers. We followed the dynamics and magnitude of spike-specific immunity in convalescents during the spontaneous course over ≥ 9 months, after SARS-CoV-2 re-exposure and after BNT162b2 mRNA vaccination. Virus-neutralizing antibodies and spike-specific T cell responses with predominance of IL-2-secreting polyfunctional CD4 T cells continuously declined over 9 months, but remained detectable at low levels. After a single vaccination, convalescents simultaneously mounted strong antibody and T cell responses against the SARS-CoV-2 spike proteins. In naïve individuals, a prime vaccination induced preferentially IL-2-secreting CD4 T cells that preceded production of spike-specific virus-neutralizing antibodies after boost vaccination. Response to vaccination, however, was not homogenous. Compared to four individuals among 455 naïve vaccinees (0.9%), we identified 5/82 (6.1%) convalescents with a delayed response to vaccination. These convalescents had originally developed dysfunctional spike-specific immune responses after SARS-CoV-2 infection, and required prime and boost vaccination to develop strong spike-specific immunity. Importantly, during the second wave of the COVID-19 pandemic in fall/winter of 2021 and prior to vaccination we detected a surge of virus-neutralizing antibodies consistent with re-exposure to SARS-CoV-2 in 6 out of 82 convalescents. The selective increase in virus-neutralizing antibodies occurred without systemic re-activation of spike-specific T cell immunity, whereas a single BNT162b2 mRNA vaccination sufficed to induce strong spike-specific antibody and systemic T cell responses in the same individuals. These results support the notion that BNT162b2 mRNA vaccination synchronizes spike-specific immunity in all convalescents of mild SARS-CoV-2 infection and may provide additional protection from re-infection by inducing more rigorous stimulation of spike-specific T cell immunity than re-exposure with SARS-CoV-2.

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

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]

scholarly journals Virus-Induced CD8+ T-Cell Immunity and Its Exploitation to Contain the SARS-CoV-2 Pandemic

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 922
Author(s):  
Maurizio Federico
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Clinical Evidence ◽  
Viral Infections ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Great Promise ◽  
Vaccine Platform ◽  
Cell Immunity

The current battle against Severe Acute Respiratory Syndrome (SARS)-Coronavirus-2 benefits from the worldwide distribution of different vaccine formulations. All anti-SARS-CoV-2 vaccines in use are conceived to induce anti-Spike neutralizing antibodies. However, this strategy still has unresolved issues, the most relevant of which are: (i) the resistance to neutralizing antibodies of emerging SARS-CoV-2 variants and (ii) the waning of neutralizing antibodies. On the other hand, both pre-clinical evidence and clinical evidence support the idea that the immunity sustained by antigen-specific CD8+ T lymphocytes can complement and also surrogate the antiviral humoral immunity. As a distinctive feature, anti-SARS-CoV-2 CD8+ T-driven immunity maintains its efficacy even in the presence of viral protein mutations. In addition, on the basis of data obtained in survivors of the SARS-CoV epidemic, this immunity is expected to last for several years. In this review, both the mechanisms and role of CD8+ T-cell immunity in viral infections, particularly those induced by SARS-CoV and SARS-CoV-2, are analyzed. Moreover, a CD8+ T-cell-based vaccine platform relying on in vivo engineered extracellular vesicles is described. When applied to SARS-CoV-2, this strategy was proven to induce a strong immunogenicity, holding great promise for its translation into the clinic.

Arenavirus-based vector platform for massive tumor self-antigen-specific CD8 T cell immunity.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14297-e14297
Author(s):  
Klaus Karl Orlinger ◽  
Weldy V. Bonilla ◽  
Sandra M Kallert ◽  
Nicole Kirchhammer ◽  
Anna-Friederike Marx ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
Genetically Engineered ◽  
T Cell Immunity ◽  
T Cell Epitopes ◽  
Cell Immunity

e14297 Background: The induction of powerful CD8+ T cell immunity to tumor associated self-antigens (TAAs) represents a critical yet challenging goal. Here we report on the development of an arenavirus-based delivery platform meeting this challenge. Previously we have shown that genetically engineered replication-attenuated lymphocytic choriomeningitis virus (LCMV) vectors, TheraT(LCMV), induce strong TAA-specific CD8 T cell immunity, but these responses can not be substantially augmented upon TheraT(LCMV) readministration. Counter to expectations, vector-neutralizing antibodies were not accountable for limited homologous prime-boosting capacity. Instead, dominant viral backbone-reactive CD8+ T cells competed against subdominant TAA-specific responses, limiting their magnitude. Methods: Herein we engineered and characterized delivery systems based on the arenaviruses Mopeia, Candid#1 and Pichinde (TheraT(MOP), TheraT(CAND), TheraT(PIC)). Results: We demonstrate that heterologous TheraT(CAND) – TheraT(LCMV) and TheraT(PIC)-TheraT(LCMV) prime-boost substantially augment TAA-specific CD8 T cell responses by rendering them immunodominant. Accordingly, intravenous administration of mice triggered up to 50% TAA epitope-specific CD8+ T cells and cured established tumors. Conversely, TheraT(MOP) – TheraT(LCMV) prime-boost was poorly immunogenic owing to cross-reactive T cell epitopes in the respective viral backbones. Conclusions: These findings establish heterologous arenavirus prime-boost combinations as a powerful new modality in tumor immunotherapy and highlight CD8 T cell epitope dominance as a significant hurdle to overcome in the vectored delivery of TAAs.

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