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Molecular & Cellular Proteomics : MCP 2021The approach of peptide-based anticancer vaccination has proven the ability to induce cancer-specific immune responses in multiple studies for various cancer entities.... (Review)
Review
The approach of peptide-based anticancer vaccination has proven the ability to induce cancer-specific immune responses in multiple studies for various cancer entities. However, clinical responses remain so far limited to single patients and broad clinical applicability was not achieved. Therefore, further efforts are required to improve peptide vaccination in order to integrate this low-side-effect therapy into the clinical routine of cancer therapy. To design clinically effective peptide vaccines in the future, different issues have to be addressed and optimized comprising antigen target selection as well as choice of optimal adjuvants and vaccination schedules. Furthermore, the combination of peptide-based vaccines with other immuno- and molecular targeted therapies as well as the development of predictive biomarkers could further improve efficacy. In this review, current approaches in the development of peptide-based vaccines and critical implications for optimal vaccine design are discussed.
Topics: Adjuvants, Immunologic; Antigens; Biomarkers; Cancer Vaccines; Humans; Neoplasms; Vaccines, Subunit
PubMed: 33583769
DOI: 10.1074/mcp.R120.002309 -
Frontiers in Immunology 2022Adjuvants are indispensable components of vaccines for stimulating optimal immune responses to non-replicating, inactivated and subunit antigens. Eliciting balanced... (Review)
Review
Adjuvants are indispensable components of vaccines for stimulating optimal immune responses to non-replicating, inactivated and subunit antigens. Eliciting balanced humoral and T cell-mediated immunity is paramount to defend against diseases caused by complex intracellular pathogens, such as tuberculosis, malaria, and AIDS. However, currently used vaccines elicit strong antibody responses, but poorly stimulate CD8 cytotoxic T lymphocyte (CTL) responses. To elicit potent CTL memory, vaccines need to engage the cross-presentation pathway, and this requirement has been a crucial bottleneck in the development of subunit vaccines that engender effective T cell immunity. In this review, we focus on recent insights into DC cross-presentation and the extent to which clinically relevant vaccine adjuvants, such as aluminum-based nanoparticles, water-in oil emulsion (MF59) adjuvants, saponin-based adjuvants, and Toll-like receptor (TLR) ligands modulate DC cross-presentation efficiency. Further, we discuss the feasibility of using carbomer-based adjuvants as next generation of adjuvant platforms to elicit balanced antibody- and T-cell based immunity. Understanding of the molecular mechanism of DC cross-presentation and the mode of action of adjuvants will pave the way for rational design of vaccines for infectious diseases and cancer that require balanced antibody- and T cell-based immunity.
Topics: Adjuvants, Immunologic; Adjuvants, Vaccine; Cross-Priming; T-Lymphocytes, Cytotoxic; Vaccines, Subunit
PubMed: 35979365
DOI: 10.3389/fimmu.2022.940047 -
Expert Review of Vaccines Dec 2017Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing... (Review)
Review
Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.
Topics: Chickenpox; Chickenpox Vaccine; Clinical Trials as Topic; Drug Approval; Drug Discovery; Herpes Zoster; Herpes Zoster Vaccine; Humans; Product Surveillance, Postmarketing; Treatment Outcome; Vaccines, Attenuated; Vaccines, Subunit
PubMed: 29047317
DOI: 10.1080/14760584.2017.1394843 -
Proceedings of the National Academy of... Aug 2014Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century,...
Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
Topics: Cell Culture Techniques; Genetic Engineering; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Reassortant Viruses; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated; Vaccines, Subunit; Viral Vaccines
PubMed: 25136134
DOI: 10.1073/pnas.1400472111 -
Current Issues in Molecular Biology 2021Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of... (Review)
Review
Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of enormous preclinical and clinical research. A live viral vaccine for prevention of chickenpox and a subunit therapeutic vaccine to prevent zoster are highly successful. In contrast, progress towards the development of effective prophylactic or therapeutic vaccines against HSV-1 and HSV-2 has met with limited success. This review provides an overview of the successes and failures, the different types of immune responses elicited by various vaccine modalities, and the need to reconsider the preclinical models and immune correlates of protection against HSV.
Topics: Alphaherpesvirinae; Animals; Herpesviridae Infections; Humans; Immunity; Vaccines, Attenuated; Vaccines, Subunit; Viral Vaccines
PubMed: 32963118
DOI: 10.21775/cimb.041.469 -
Molecules (Basel, Switzerland) Jan 2021Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein... (Review)
Review
Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.
Topics: Amino Acids; Anti-Infective Agents; Antiviral Agents; Computer Simulation; Cosmeceuticals; Dietary Supplements; Gene Transfer Techniques; Humans; Lactoferrin; Lipid Bilayers; Nanostructures; Peptides; Stem Cells; Vaccines, Subunit; COVID-19 Drug Treatment
PubMed: 33467522
DOI: 10.3390/molecules26020430 -
Journal of Immunology Research 2018
Topics: Animals; B-Lymphocytes; Humans; Immunity; Immunization; Immunodominant Epitopes; Immunotherapy; Infections; T-Lymphocytes; Vaccines, Subunit
PubMed: 30116752
DOI: 10.1155/2018/4568239 -
Nature Mar 2014In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these...
In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes. Here we translate this 'albumin hitchhiking' approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.
Topics: Animals; Base Sequence; CpG Islands; Female; Lymph Nodes; Mice; Mice, Inbred C57BL; T-Lymphocytes; Vaccines, Subunit; Vaccines, Synthetic
PubMed: 24531764
DOI: 10.1038/nature12978 -
The New England Journal of Medicine Jun 2022The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials.
METHODS
We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose.
RESULTS
Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2.
CONCLUSIONS
In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).
Topics: Adolescent; Adult; COVID-19; COVID-19 Vaccines; Double-Blind Method; Humans; SARS-CoV-2; Vaccination; Vaccines; Vaccines, Subunit; Young Adult
PubMed: 35507481
DOI: 10.1056/NEJMoa2202261 -
ACS Applied Bio Materials Mar 2022This review discusses peptide epitopes used as antigens in the development of vaccines in clinical trials as well as future vaccine candidates. It covers peptides used... (Review)
Review
This review discusses peptide epitopes used as antigens in the development of vaccines in clinical trials as well as future vaccine candidates. It covers peptides used in potential immunotherapies for infectious diseases including SARS-CoV-2, influenza, hepatitis B and C, HIV, malaria, and others. In addition, peptides for cancer vaccines that target examples of overexpressed proteins are summarized, including human epidermal growth factor receptor 2 (HER-2), mucin 1 (MUC1), folate receptor, and others. The uses of peptides to target cancers caused by infective agents, for example, cervical cancer caused by human papilloma virus (HPV), are also discussed. This review also provides an overview of model peptide epitopes used to stimulate non-specific immune responses, and of self-adjuvanting peptides, as well as the influence of other adjuvants on peptide formulations. As highlighted in this review, several peptide immunotherapies are in advanced clinical trials as vaccines, and there is great potential for future therapies due the specificity of the response that can be achieved using peptide epitopes.
Topics: Adjuvants, Immunologic; Animals; Antigens; Cancer Vaccines; Communicable Disease Control; Humans; Neoplasms; Peptides; Vaccine Development; Vaccines, Subunit
PubMed: 35195008
DOI: 10.1021/acsabm.1c01238