bims-inflim 2018-04-29 papers

Issue of 2018–04–29
four papers selected by
Christine Oshansky-Weilnau

Vaccine. 2018 Apr 18. pii: S0264-410X(18)30486-9. [Epub ahead of print]

Responses to live attenuated influenza vaccine in children vaccinated previously with Pandemrix (ASO3B adjuvanted pandemic A/H1N1pdm09).

Katja Höschler, Jo Southern, Catherine Thompson, Fiona Warburton, Nick J Andrews, Elizabeth Miller, Maria Zambon.

BACKGROUND: We report a phase III/IV open-label study on the immunogenicity of a single dose of a Live Attenuated Influenza Vaccine (LAIV) (Fluenz™) in children naïve to, or in previous receipt of, AS03B adjuvanted A/H1N1pdm09 influenza vaccine (Pandemrix™), to investigate whether early exposure to an adjuvanted subunit influenza vaccine impacts on subsequent response to quadrivalent LAIV (qLAIV).
METHOD AND FINDINGS: Eligible children were enrolled to receive qLAIV and stratified according to previous Pandemrix™ vaccination. Functional antibody for the vaccine strains were analysed using Haemagglutination Inhibition (HAI); in addition antibodies to the A/H1N1pdm09 strain were measured by Neuraminidase Antibody Inhibition (NAI) and neutralisation assays. Fourfold titre increases by HAI were observed for 39% (95% confidence interval 33-46%) and 43% (37-51%) of subjects for the two influenza B vaccine strains and 8% (5-13%) for the A/H3N2 strain with no significant differences between the Pandemrix™ naïve or previously vaccinated groups in antibody tites pre- or post-vaccination or seroconversion rates. In both groups, the response to the qLAIV A/H1N1pdm09 component was barely detectable, overall HAI seroconversion rate 1.8% (0.5-4.7%). Previous receipt of Pandemrix™ was associated with significantly higher levels of A/H1N1pdm09 neutralising antibody, but decreased NAI titres pre-vaccination, with the differences maintained post-vaccination.
CONCLUSION: Previous receipt of Pandemrix™ has had a significant impact on the influenza immune status of children several years later. Higher levels of neutralising antibody to A/H1N1pdm09 pre- and post-vaccination, but significantly lower levels of antibody to NA, were observed compared with Pandemrix™-naïve children, while responses to influenza B and A/H3N2 and antibody levels prior to vaccination were similar in both groups. This suggests that early vaccination with a powerful adjuvant maintains functional immunity for several years, which prevents natural infection. Alternatively, the AS03B adjuvant may have re-directed the immune response, with focus towards viral HA and away from viral NA.

Keywords: Childhood; Cross-reactive effects; Influenza; Oil-in-water adjuvant; Vaccine

DOI: https://doi.org/10.1016/j.vaccine.2018.04.017

Microbes Infect. 2018 Apr 18. pii: S1286-4579(18)30093-5. [Epub ahead of print]

Dissecting host cell death programs in the pathogenesis of influenza.

Jeffrey Downey, Erwan Pernet, François Coulombe, Maziar Divangahi.

Influenza A virus (IAV) is a pulmonary pathogen, responsible for significant yearly morbidity and mortality. Due to the absence of highly effective antiviral therapies and vaccine, as well as the constant threat of an emerging pandemic strain, there is considerable need to better understand the host-pathogen interactions and the factors that dictate a protective versus detrimental immune response to IAV. Even though evidence of IAV-induced cell death in human pulmonary epithelial and immune cells has been observed for almost a century, very little is known about the consequences of cell death on viral pathogenesis. Recent study indicates that both the type of cell death program and its kinetics have major implications on host defense and survival. In this review, we focus on cell death programs induced in influenza-infected cells and provide insight into its the immunological consequences, in hopes of fostering new areas of investigation for targeted clinical intervention.

Keywords: Alveolar Epithelial Cells; Apoptosis; Cell Death Program; Influenza A Virus; Necroptosis; Pulmonary Macrophages

DOI: https://doi.org/10.1016/j.micinf.2018.03.005

Curr Opin Immunol. 2018 Apr 19. pii: S0952-7915(17)30192-9. [Epub ahead of print]53 51-57

Development of next generation hemagglutinin-based broadly protective influenza virus vaccines.

Raffael Nachbagauer, Peter Palese.

Influenza viruses are a severe threat to human health and current vaccines do not provide sufficient protection. The highly variable nature of influenza viruses has made the production of efficacious vaccines a challenge. In recent years, a multitude of novel, broadly reactive influenza virus vaccination approaches have been described. What has long seemed impossible could now become reality in the near future-a new generation of influenza virus vaccines that provides long-lasting and broad protection against seasonal as well as potentially pandemic influenza virus strains. This review will discuss new hemagglutinin-based vaccines and their current stage of development.

DOI: https://doi.org/10.1016/j.coi.2018.04.001

Trends Immunol. 2018 Apr 18. pii: S1471-4906(18)30059-0. [Epub ahead of print]

Recasting Human Vδ1 Lymphocytes in an Adaptive Role.

Martin S Davey, Carrie R Willcox, Alfie T Baker, Stuart Hunter, Benjamin E Willcox.

γδ T cells are unconventional lymphocytes commonly described as 'innate-like' in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges. Concomitantly, they differentiate from a Vδ1 T cell naïve (Tnaïve) to a Vδ1 T cell effector (Teffector) phenotype, marked by the downregulation of lymphoid homing receptors and upregulation of peripheral homing receptors and effector markers. This suggests that an adaptive paradigm applies to Vδ1 T cells, likely involving TCR-dependent but MHC-unrestricted responses to microbial and non-microbial challenges.

DOI: https://doi.org/10.1016/j.it.2018.03.003