T cell-based strategies for HIV-1 vaccines.
Ontology highlight
ABSTRACT:
SUBMITTER: Korber B
PROVIDER: S-EPMC7227724 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:After nearly four decades of research, a safe and effective HIV-1 vaccine remains elusive. There are many reasons why the development of a potent and durable HIV-1 vaccine is challenging, including the extraordinary genetic diversity of HIV-1 and its complex mechanisms of immune evasion. HIV-1 envelope glycoproteins are poorly recognized by the immune system, which means that potent broadly neutralizing antibodies (bnAbs) are only infrequently induced in the setting of HIV-1 infection or through vaccination. Thus, the biology of HIV-1-host interactions necessitates novel strategies for vaccine development to be designed to activate and expand rare bnAb-producing B cell lineages and to select for the acquisition of critical improbable bnAb mutations. Here we discuss strategies for the induction of potent and broad HIV-1 bnAbs and outline the steps that may be necessary for ultimate success.
| S-EPMC9372928 | biostudies-literature
Project description:Dendritic cells (DCs) are potent inducers of adaptive immunity and their clinical use in cancer vaccine formulations remains an area of active translational and clinical investigation. Although cancer vaccines applied as monotherapies have had a modest history of clinical success, there is great enthusiasm for novel therapeutic strategies combining DC-based cancer vaccines with agents that 'normalize' immune function in the tumor microenvironment (TME). Broadly, these combination vaccines are designed to antagonize/remove immunosuppressive networks within the TME that serve to limit the antitumor action of vaccine-induced T cells and/or to condition the TME to facilitate the recruitment and optimal function and durability of vaccine-induced T cells. Such combination regimens are expected to dramatically enhance the clinical potency of DC-based cancer vaccine platforms.
| S-EPMC5619021 | biostudies-literature
Project description:Peptides vaccination is an interesting approach to activate T-cells toward desired antigens in hematological malignancies. In addition to classical tumor associated antigens, such as cancer testis antigens, new potential targets for peptide vaccination comprise neo-antigens including JAK2 and CALR mutations, and antigens from immune regulatory proteins in the tumor microenvironment such as programmed death 1 ligands (PD-L1 and PD-L2). Immunosuppressive defenses of tumors are an important challenge to overcome and the T cell suppressive ligands PD-L1 and PD-L2 are often present in tumor microenvironments. Thus, PD-L1 and PD-L2 are interesting targets for peptide vaccines in diseases where the tumor microenvironment is known to play an essential role such as multiple myeloma and follicular lymphoma. In myelodysplastic syndromes the drug azacitidine re-exposes tumor associated antigens, why vaccination with related peptides would be an interesting addition. In myeloproliferative neoplasms the JAK2 and CALR mutations has proven to be immunogenic neo-antigens and thus possible targets for peptide vaccination. In this mini review we summarize the basis for these novel approaches, which has led to the initiation of clinical trials with various peptide vaccines in myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and follicular lymphoma.
| S-EPMC6174926 | biostudies-literature
Project description:The prevalence of the coronavirus disease 2019 (COVID-19) pandemic in its second year has led to massive global human and economic losses. The high transmission rate and the emergence of diverse SARS-CoV-2 variants demand rapid and effective approaches to preventing the spread, diagnosing on time, and treating affected people. Several COVID-19 vaccines are being developed using different production systems, including plants, which promises the production of cheap, safe, stable, and effective vaccines. The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. Currently, two plant-based COVID-19 vaccine candidates, coronavirus virus-like particle (CoVLP) and Kentucky Bioprocessing (KBP)-201, are in clinical trials, and many more are in the preclinical stage. Interim phase 2 clinical trial results have revealed the high safety and efficacy of the CoVLP vaccine, with 10 times more neutralizing antibody responses compared to those present in a convalescent patient's plasma. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far.
| S-EPMC8473425 | biostudies-literature
Project description:IntroductionPromising HIV vaccine candidates are steadily progressing through the clinical trial pipeline. Once available, HIV vaccines will be an important complement but also potential competitor to other biomedical prevention tools such as pre-exposure prophylaxis (PrEP). Accordingly, the value of HIV vaccines and the policies for rollout may depend on that interplay and tradeoffs with utilization of existing products. In this economic modelling analysis, we estimate the cost-effectiveness of HIV vaccines considering their potential interaction with PrEP and condom use.MethodsWe developed a dynamic model of HIV transmission among the men who have sex with men population (MSM), aged 15-64 years, in Seattle, WA offered PrEP and HIV vaccine over a time horizon of 2025-2045. A healthcare sector perspective with annual discount rate of 3% for costs (2017 USD) and quality-adjusted life years (QALYs) was used. The primary economic endpoint is the incremental cost-effectiveness ratio (ICER) when compared to no HIV vaccine availability.ResultsHIV vaccines improved population health and increased healthcare costs. Vaccination campaigns achieving 90% coverage of high-risk men and 60% coverage of other men within five years of introduction are projected to avoid 40% of new HIV infections between 2025 and 2045. This increased total healthcare costs by $30 million, with some PrEP costs shifted to HIV vaccine spending. HIV vaccines are estimated to have an ICER of $42,473/QALY, considered cost-effective using a threshold of $150,000/QALY. Results were most sensitive to HIV vaccine efficacy and future changes in the cost of PrEP drugs. Sensitivity analysis found ranges of 30-70% HIV vaccine efficacy remained cost-effective. Results were also sensitive to reductions in condom use among PrEP and vaccine users.ConclusionsAccess to an HIV vaccine is desirable as it could increase the overall effectiveness of combination HIV prevention efforts and improve population health. Planning for the rollout and scale-up of HIV vaccines should carefully consider the design of policies that guide interactions between vaccine and PrEP utilization and potential competition.
| S-EPMC6689690 | biostudies-literature
Project description:BACKGROUND: HIV vaccine development must address the genetic diversity and plasticity of the virus that permits the presentation of diverse genetic forms to the immune system and subsequent escape from immune pressure. Assessment of potential HIV strain coverage by candidate T cell-based vaccines (whether natural sequence or computationally optimized products) is now a critical component in interpreting candidate vaccine suitability. METHODS: We have utilized an N-mer identity algorithm to represent T cell epitopes and explore potential coverage of the global HIV pandemic using natural sequences derived from candidate HIV vaccines. Breadth (the number of T cell epitopes generated) and depth (the variant coverage within a T cell epitope) analyses have been incorporated into the model to explore vaccine coverage requirements in terms of the number of discrete T cell epitopes generated. RESULTS: We show that when multiple epitope generation by a vaccine product is considered a far more nuanced appraisal of the potential HIV strain coverage of the vaccine product emerges. By considering epitope breadth and depth several important observations were made: (1) epitope breadth requirements to reach particular levels of vaccine coverage, even for natural sequence-based vaccine products is not necessarily an intractable problem for the immune system; (2) increasing the valency (number of T cell epitope variants present) of vaccine products dramatically decreases the epitope requirements to reach particular coverage levels for any epidemic; (3) considering multiple-hit models (more than one exact epitope match with an incoming HIV strain) places a significantly higher requirement upon epitope breadth in order to reach a given level of coverage, to the point where low valency natural sequence based products would not practically be able to generate sufficient epitopes. CONCLUSIONS: When HIV vaccine sequences are compared against datasets of potential incoming viruses important metrics such as the minimum epitope count required to reach a desired level of coverage can be easily calculated. We propose that such analyses can be applied early in the planning stages and during the execution phase of a vaccine trial to explore theoretical and empirical suitability of a vaccine product to a particular epidemic setting.
| S-EPMC3284408 | biostudies-literature
Project description:Landmark successes in oncoimmunology have led to development of therapeutics boosting the host immune system to eradicate local and distant tumors with impactful tumor reduction in a subset of patients. However, current immunotherapy modalities often demonstrate limited success when involving immunologically cold tumors and solid tumors. Here, we describe the role of various biomaterials to formulate cancer vaccines as a form of cancer immunotherapy, seeking to utilize the host immune system to activate and expand tumor-specific T cells. Biomaterial-based cancer vaccines enhance the cancer-immunity cycle by harnessing cellular recruitment and activation against tumor-specific antigens. In this review, we discuss biomaterial-based vaccine strategies to induce lymphocytic responses necessary to mediate anti-tumor immunity. We focus on strategies that selectively attract dendritic cells via immunostimulatory gradients, activate them against presented tumor-specific antigens, and induce effective cross-presentation to T cells in secondary lymphoid organs, thereby generating immunity. We posit that personalized cancer vaccines are promising targets to generate long-term systemic immunity against patient- and tumor-specific antigens to ensure long-term cancer remission.
| S-EPMC8725170 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) has infected 76 million people and killed an estimated 35 million. During its 40-year history, remarkable progress has been made on antiretroviral drugs. Progress toward a vaccine has also been made, although this has yet to deliver a licensed product. In 2007, I wrote a review, HIV AIDS Vaccines: 2007. This review, HIV AIDS Vaccines: 2018, focuses on the progress in the past 11 years. I begin with key challenges for the development of an AIDS vaccine and the lessons learned from the six completed efficacy trials, only one of which has met with some success.
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Project description:An anti-malarial vaccine against the extremely lethal Plasmodium falciparum is desperately needed. Peptides from this parasite's proteins involved in invasion and having high red blood cell-binding ability were identified; these conserved peptides were not immunogenic or protection-inducing when used for immunizing Aotus monkeys. Modifying some critical binding residues in these high-activiy binding peptides' (HABPs') attachment to red blood cells (RBC) allowed them to induce immunogenicity and protection against experimental challenge and acquire the ability to bind to specific HLA-DRp1* alleles. These modified HABPs adopted certain characteristic structural configurations as determined by circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) associated with certain HLA-DRbeta1* haplotype binding activities and characteristics, such as a 2-angstroms-distance difference between amino acids fitting into HLA-DRp1 Pockets 1 to 9, residues participating in binding to HLA-DR pockets and residues making contact with the TCR, suggesting haplotype and allele-conscious TCR. This has been demonstrated in HLA-DR-like genotyped monkeys and provides the basis for designing high effective, subunit-based, multi-antigen, multi-stage, synthetic vaccines, for immediate human use, malaria being one of them.
| S-EPMC4506160 | biostudies-literature
Project description:The past decade has seen tremendous developments in novel cancer therapies through the targeting of tumor-cell-intrinsic pathways whose activity is linked to genetic alterations and the targeting of tumor-cell-extrinsic factors, such as growth factors. Furthermore, immunotherapies are entering the clinic at an unprecedented speed after the demonstration that T cells can efficiently reject tumors and that their antitumor activity can be enhanced with antibodies against immune-regulatory molecules (checkpoint blockade). Current immunotherapy strategies include monoclonal antibodies against tumor cells or immune-regulatory molecules, cell-based therapies such as adoptive transfer of ex-vivo-activated T cells and natural killer cells, and cancer vaccines. Herein, we discuss the immunological basis for therapeutic cancer vaccines and how the current understanding of dendritic cell and T cell biology might enable the development of next-generation curative therapies for individuals with cancer.
| S-EPMC3788678 | biostudies-literature