Exploring vaccine potency of recombinant protein-based nanoparticles
Abstract
Vaccination can be an effective defense against many infectious diseases. Controlling and suppressing viral infection is highly dependent on vaccines, as there are not a variety of drugs that can suppress disease caused by viral infection. Vaccines have been developed in a variety of forms, from the classically inactivated vaccines to the recent mRNA-based vaccines. Although not yet commercially approved, a virus-like particle vaccine in the form of nanoparticles expressing recombinant antigenic protein is emerging as a good candidate.
In this presentation, we will discuss how an understanding of the immune system can inform the design of nanoparticle vaccines and attempts to fabricate several forms of recombinant protein-based nanoparticles and discuss their vaccine efficacy.
Targeting age-associated defects in T cell responses for vaccine development Targeting defective T cell responses in older individuals to improve
Abstract
Generation of protective T cell responses declines with age, leading to increased susceptibility to infections such as with SARS-CoV-2 virus and poor protective efficacy to vaccination. Studies have examined age-associated changes in microRNA networks causing this defect. Increased miR-21 expression in aged naïve T cells results in sustained activation of multiple signaling pathways, which favors the differentiation of hyper-inflammatory effector cells over stem-like memory precursor cells. Another example is the reduced expression of miR-181a in naïve T cells from older individuals. We show that miR-181ab1 deficiency in peripheral murine T cells causes defective T cell expansion and delayed viral clearance after acute infection, resembling human immune aging. Naïve T cells from older individuals as well as miR-181ab1-deficient murine T cells develop excessive replication stress after activation, due to reduced histone expression and delayed S-phase cell cycle progression. Reduced histone expression is caused by the miR-181a target SIRT1. Inhibition of SIRT1 activity increases histone expression and diminishes replication stress in replicating T cells from old individuals. Correspondingly, treatment with SIRT1 inhibitors improves viral clearance in miR-181a-deficient mice after infection. Therefore, SIRT1 inhibition may be beneficial to treat systemic viral infection in older individuals.
Advanced adjuvant strategies for protein-based vaccine development
Abstract
Whole virus vaccines, especially live attenuated vaccines, are efficient to stimulate immune responses against pathogenic infection. However, immunogenicity and safety generally have a negative (inverse?) correlation. Proein-based vaccines are obiously advantageous in safety issues but it naturally has problem with immunogenicity. To enhance immune response to protein antigens, the vaccine is prepared mixed antigen/adjuvant formulation. Adjuvant not only strengthen the immune response but also dramatically affects the character of antigen-specific immune responses. Many of new adjuvant mimics microbial components as these molecules are target of innate immune system and they can induce better cell-mediated immune responses, which are especially important to prevent viral infectious diseases. Understand of mechanism involved in the action of new adjuvants is important to secure the safety of vaccination. It will also provide a better opportunity to develop more efficient vaccines against broader-spectrum of infectious diseases.
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