PND-1186 Neuraminidase inhibitors NAI are the most frequentl

Neuraminidase inhibitors (NAI) are the most frequently used antiviral drug for management of influenza infection. Early NAI treatment was associated with shorter illness duration, and is most beneficial when treatment started within 2days of illness onset (Lee et al., 2015). However, except for induction of resistant strains, NAI treatment can not reverse the immune mediated tissue damage triggered by infection. Peramivir used in this study is an effective NAI against a variety of influenza A and B subtypes. The results suggested that both 1,6-bis PC and peramivir can improve mortality and illness severity in mice infected with lethal influenza infection. However, high-dose treatment of 1,6-bis PC had better efficiency than peramivir; combinated treatment with 1,6-bis PC and peramivir yield even better efficiency. Previous studies suggested that lethal dissemination of influenza virus is associated with dysregulation of PND-1186 (Cilloniz et al., 2010), and immune mediated tissue damage may present limited sensitivity to antiviral agents after a robust host innate immune response was triggered (Sidwell et al., 1999; Yen et al., 2005; Govorkova et al., 2009). Our results indicated that CRP may link to proinflammatory mediators contributing to activation of complement and boosting inflammatory response in severe influenza infections.
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Introduction As the only vaccine for tuberculosis (TB), Mycobacterium bovis Bacillus Calmette-Guerin (BCG) has a high annual coverage in up to 90% infants worldwide. While providing effective protection for children against tuberculous meningitis and miliary TB, BCG protection persists for only about 15years (Mangtani et al., 2014) and is insufficient to thwart the reactivation of latent tuberculosis infection (LTBI), which is often the cause of adult pulmonary TB (Andersen and Doherty, 2005). The World Health Organization (WHO) estimated that one-third of the world\'s population harbors LTBI, and that 10% these individuals will progress to active pulmonary TB resulting from the endogenous reactivation of the latent Mycobacterium tuberculosis persisting (WHO, 2015). This is especially true in people co-infected with M. tuberculosis and human immunodeficiency virus (WHO, 2015, 2016). Approximately 10 million new cases of TB occur annually, mostly in adults (WHO, 2016). Therefore, there is an urgent need to develop an efficacious vaccine for better control of LTBI and adult TB. TB subunit vaccines have defined compositions and are safe, and so have attracted extensive attention compared to attenuated M. tuberculosis strains, recombinant BCG strains, DNA, and viral vectors (Kaufmann, 2014). Novel candidates have been evaluated in clinical trials designed to assess their prophylactic potential use. The candidates were constructed conventionally based on antigens secreted by logarithmically growing M. tuberculosis, such as the antigen85 complex, ESAT-6 protein, and TB10.4 protein (Kaufmann, 2014). In particular, the heat shock protein X (HspX), which is characteristically expressed by M. tuberculosis growing under low O2 condition, was demonstrated to enhance BCG-induced protection against primary TB infection in a mouse model (Shi et al., 2010). Subsequently, the construction of two-stage subunits ID93 (Rv3619-Rv1813-Rv3620-Rv2608; Bertholet et al., 2010) or H56 (Ag85B-ESAT-6-Rv2660c; Aagaard et al., 2011) was accomplished by fusing secreted and latent antigens of M. tuberculosis. Recently, the co-existence of both actively growing and latent M. tuberculosis strains in LTBIs and patients with active TB (ATB) infections were reported (Wang et al., 2015; Ma et al., 2016). A multistage subunit designated WH121 contains fusion polypeptide comprised of antigens Rv3407, PhoY2, Ag85A, Rv2626c, and RpfB. These antigens are expressed in different stages of TB infection. The use of WH121 in an adjuvant preparation of DMT (DDA-MPLA-TDB) reportedly provides protection against primary TB infection that is comparable to that provided by the BCG vaccine, and also enhances the protection of BCG-primed mice against the post-exposure infection (Ma et al., 2016). However, adult TB is mainly caused by endogenous reactivation of LTBI (WHO, 2015) and the secondary transmission route is exogenous infection (Verver et al., 2005). All the TB candidate vaccines could elicit antigen-specific Th1-type immune responses and confer significant protection against primary infection in different animal models, including mice (Ma et al., 2016), monkeys (Reed et al., 2009; Lin et al., 2012; Coler et al., 2013) and humans (Luabeya et al., 2015). However, no TB vaccine devised so far can achieve sterile immunity and thus thwart the reactivation of LTBI.