Role of myeloid-derived suppressor cells in viral respiratory infections; Hints for discovering therapeutic targets for COVID-19.

The expansion of myeloid-derived suppressor cells (MDSCs), known as heterogeneous population of immature myeloid cells, is enhanced during several pathological conditions such as inflammatory or viral respiratory infections. It seems that the way MDSCs behave in infection depends on the type and the virulence mechanisms of the invader pathogen, the disease stage, and the infection-related pathology. Increasing evidence showing that in correlation with the severity of the disease, MDSCs are accumulated in COVID-19 patients, in particular in those at severe stages of the disease or ICU patients, contributing to pathogenesis of SARS-CoV2 infection. Based on the involved subsets, MDSCs delay the clearance of the virus through inhibiting T-cell proliferation and responses by employing various mechanisms such as inducing the secretion of anti-inflammatory cytokines, inducible nitric oxide synthase (iNOS)-mediated hampering of IFN-γ production, or forcing arginine shortage. While the immunosuppressive characteristic of MDSCs may help to preserve the tissue homeostasis and prevent hyperinflammation at early stages of the infection, hampering of efficient immune responses proved to exert significant pathogenic effects on severe forms of COVID-19, suggesting the targeting of MDSCs as a potential intervention to reactivate T-cell immunity and thereby prevent the infection from developing into severe stages of the disease. This review tried to compile evidence on the roles of different subsets of MDSCs during viral respiratory infections, which is far from being totally understood, and introduce the promising potential of MDSCs for developing novel diagnostic and therapeutic approaches, especially against COVID-19 disease.

In silico prediction of B and T cell epitopes based on NDV fusion protein for vaccine development against Newcastle disease virus.

Newcastle disease (ND) is known as the most common diseases of economic importance worldwide. Vaccination against virulent strains of Newcastle disease virus (NDV) has failed during some outbreaks. Here, we aimed to assess the epitopes of NDV fusion protein as targets for a peptide-based vaccine. To explore the most antigenic epitopes on the F protein, we retrieved virulent strains of genotype VII from National Center for Biotechnology Information (NCBI). Linear and conformational B-cell epitopes were identified. Moreover, T-cell epitopes with high and moderate binding affinities to human major histocompatibility complex (MHC) class I and class II alleles were predicted using bioinformatics tools. Subsequently, the overlapped epitopes of B-cell and MHC class I and MHC class II were determined. To validate our predictions, the best epitopes were docked, to chicken MHC class I (B-F) alleles using the HADDOCK flexible docking server. Seven 'high ranked epitopes' were identified. Among them, 'LYCTRIVTF' and 'MRATYLETL' showed the highest scores. The other five epitopes including LSGEFDATY, LTTPPYMALK, LYLTELTTV, DCIKITQQV and SIAATNEAV obtained very encouraging results as well. SIAATNEAV had been recognized as a neutralizing epitope of F protein using monoclonal antibodies before. Taken together, our results demonstrated that the identified epitopes needed to be tested by in vitro and in vivo experiments.

Influenza vaccine: Where are we and where do we go?

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.