Τετάρτη 21 Αυγούστου 2019

Vaccines


  • An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice

    Posted:2019-08-05
    npj Vaccines, Published online: 05 August 2019; doi:10.1038/s41541-019-0122-8
    The BCG vaccine is widely used but has highly variable efficacy due at least in part to its inefficient processing by antigen-presenting cells (APC). Chinnaswamy Jagannath and colleagues at the University of Texas Health Sciences Center identify a peptide (C5) derived from the Mycobacterium tuberculosis (Mtb) virulence factor component CFP10 which can efficiently enhance BCG’s ability to activate APC function. C5’s activity in APCs is dependent on both Toll-like receptor 2 signaling and activation of autophagy which together enhances presentation of the Mtb protein Ag85B. A recombinant BCG vaccine over-expressing both Ag85B and C5 (BCG85C5) more strongly activates TH1-like responses which are known to be protective against Mtb infection. Mouse vaccination with BCG85C5 induces a qualitatively and quantitatively superior response to BCG—including greater expansion of Ag85B-specific T cells, more robust memory T cell formation and better control of Mtb in both lung and spleen.

  • Successful application of prime and pull strategy for a therapeutic HSV vaccine

    Posted:2019-08-01
    npj Vaccines, Published online: 01 August 2019; doi:10.1038/s41541-019-0129-1
    “Prime and pull” vaccination strategies involve an initial vaccination followed by the local application of a stimulant such as chemokines to recruit immune cells to infection target areas such as the mucosa. David Bernstein and colleagues investigate the efficacy of a prime and pull approach in a guinea pig model of recurrent genital Herpes simplex virus 2 (HSV-2) infection. Animals were vaccinated with HSV-2 glycoproteins in adjuvant with or without subcutaneous or topical (vaginal) exposure to the immune stimulant imiquimod to act as the “pull”. Animals with topical imiquimod show superior control of HSV-2 infection and improved recruitment of CD8+ T cells to the vaginal epithelium. Topical application of imiquimod demonstrates better control than subcutaneous imiquimod suggesting that “pulling” might be a useful approach in HSV vaccination.

  • <i>Clostridium perfringens</i> epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein

    Posted:2019-07-30
    npj Vaccines, Published online: 30 July 2019; doi:10.1038/s41541-019-0128-2
    Cells expressing myelin and lymphocyte protein (MAL), the putative receptor for Clostridium perfringens’ epsilon toxin, can be sensitive to otherwise attenuated mutants of the toxin. Here, the team led by Richard Titball at United Kingdom’s University of Exeter found that a previous variant exhibits differential toxic effects when cells express sheep or human MAL. To circumvent this, Titball’s team applied site-directed mutagenesis of the receptor binding site to develop a new variant with enhanced reduction in toxicity towards MAL-expressing cells and able to induce high levels of neutralising antibodies upon immunisation of sheep. These findings suggests that testing genetic toxoids in cells expressing MAL from the target species might be relevant for enterotoxaemia vaccine development and warrant further studies into the role of MAL in epsilon toxin-mediated pathogenesis.

  • Epitope targeting with self-assembled peptide vaccines

    Posted:2019-07-19
    npj Vaccines, Published online: 19 July 2019; doi:10.1038/s41541-019-0125-5
    Synthetic nanoparticles have the potential to be a simple, efficacious, and customizable platform for vaccine delivery. Christopher H. Clegg and colleagues include B cell epitopes on a self-assembling α-helical peptide nanoparticle carrier in order to elicit robust antibody generation. This novel vaccine platform is validated in vivo to produce physiologically-relevant antibodies in three different settings: an antibody-mediated ‘castration’ approach (anti-gonadotropin-releasing hormone), depletion of IgE (by generation of anti-IgE), and finally production of antibodies to a conserved H1N1 influenza epitope that mediates a protective effect in mice.

  • A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains

    Posted:2019-07-19
    npj Vaccines, Published online: 19 July 2019; doi:10.1038/s41541-019-0126-4
    Flu vaccines that target the head domain of the viral hemagglutinin (HA) surface glycoprotein are highly immunogenic, yet the variable nature of this domain across viral strains and its continuous antigenic drift limit vaccine efficacy. As the HA stalk domain is conserved across influenza viruses, targeting this region is a promising strategy to generate universal flu vaccines. However, eliciting high antibody levels against the HA stalk domain and conserved regions in the head domain remains challenging. Here Peter Palese and colleagues at Mount Sinai develop “mosaic” HAs (mHAs) aimed at eliciting antibodies targeting both the stalk domain and epitopes in the head domain outside of the major antigenic sites. These mHAs are based on antigenic silencing of the immunodominant antigenic sites of an H3 protein, which are exchanged with exotic HA sequences from avian influenza viruses. Vaccination of mice with inactivated viruses expressing mHAs induced both stalk- and head-specific antibodies active in vitro, and transfer of sera from mice immunized with mHAs was better than sera from mice immunized with a seasonal vaccine at protecting mice from heterologous challenge with viruses carrying different H3 proteins, demonstrating the potential of mHAs as universal influenza virus vaccine candidates.

  • Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females

    Posted:2019-07-12
    npj Vaccines, Published online: 12 July 2019; doi:10.1038/s41541-019-0124-6
    Males and females show pronounced differences in their immune responses. Sabra L. Klein and colleagues at Johns Hopkins University examine how sex differences in immune responses to influenza vaccination are affected by aging. Using both human volunteers and mouse models (adults vs. aged) they find that adult females have more robust interleukin-6 production and greater titers and quality of influenza-specific antibodies. Vaccination was also more protective in adult female mice. These sex differences in influenza responses are however lost in aged individuals. Gonadectomy and hormone replacement demonstrate that sex steroids exert a key influence, with estradiol positively- and testosterone negatively-correlating with influenza vaccine responses. The diminished production of estradiol in aged females and testosterone in aged males likely contributes to the equalization of influenza vaccine responses in the aged.
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