TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Influenza A virus (IAV) is a major cause of respiratory illness. Given the disease severity, associated economic costs, and recent appearance of novel IAV strains, there is a renewed interest in developing novel and efficacious "universal" IAV vaccination strategies. Recent studies have highlighted that immunizations capable of generating local (i.e., nasal mucosa and lung) tissue-resident memory T and B cells in addition to systemic immunity offer the greatest protection against future IAV encounters. Current IAV vaccines are designed to largely stimulate IAV-specific antibodies, but do not generate the lung-resident memory T and B cells induced during IAV infections. Herein, we report on an intranasally administered biocompatible polyanhydride nanoparticle-based IAV vaccine (IAV-nanovax) capable of providing protection against subsequent homologous and heterologous IAV infections in both inbred and outbred populations. Our findings also demonstrate that vaccination with IAV-nanovax promotes the induction of germinal center B cells within the lungs, both systemic and lung local IAV-specific antibodies, and IAV-specific lung-resident memory CD4 and CD8 T cells. Altogether our findings show that an intranasally administered nanovaccine can induce immunity within the lungs, similar to what occurs during IAV infections, and thus could prove useful as a strategy for providing "universal" protection against IAV.

SOLUTION: a section of the journal Frontiers in Immunology Polyanhydride Nanovaccine Induces Robust Pulmonary B and T Cell Immunity and Confers Protection Against Homologous and Heterologous Influenza A Virus Infections

PROBLEM: Redirecting the splicing machinery through the hybridization of high affinity, RNase H-incompetent oligonucleotide analogs such as phosphoramidate morpholino oligonucleotides (PMO) might lead to important clinical applications. Chemical conjugation of PMO to arginine-rich cell penetrating peptides (CPP) such as (R-Ahx-R) 4 (with Ahx standing for 6-aminohexanoic acid) leads to sequencespecific splicing correction in the absence of endosomolytic agents in cell culture at variance with most conventional CPPs. Importantly, (R-Ahx-R) 4 -PMO conjugates are effective in mouse models of various viral infections and Duchenne muscular dystrophy. Unfortunately, active doses in some applications might be close to cytotoxic ones thus presenting challenge for systemic administration of the conjugates in those clinical settings. Structureactivity relationship studies have thus been undertaken to unravel CPP structural features important for the efficient nuclear delivery of the conjugated PMO and limiting steps in their internalization pathway. Affinity for heparin (taken as a model heparan sulfate), hydrophobicity, cellular uptake, intracellular distribution and splicing correction have been monitored. Spacing between the charges, hydrophobicity of the linker between the Arg-groups and Arg-stereochemistry influence splicing correction efficiency. A significant correlation between splicing correction efficiency, affinity for heparin and ability to destabilize model synthetic vesicles has been observed but no correlation with cellular uptake has been found. Efforts will have to focus on endosomal escape since it appears to remain the limiting factor for the delivery of these splice-redirecting ON analogs.

SOLUTION: Delivery of steric block morpholino oligomers by (R-X-R) 4 peptides: structure-activity studies

PROBLEM: Coronavirus mouse hepatitis virus (MVH)-A59 causes a persistent, productive infection in primary glial cell cultures . Microbial Pathogenesis 1987 ; 3 : 79-86 . MHV-A59 causes a chronic demyelinating disease in mice which is accompanied by persistence of viral genome in white matter . As part of the investigation into the mechanism of viral persistence, infection of glial cells, probable targets for chronic infection, was studied by the use of mixed glial, enriched oligodendrocyte and enriched astrocyte cultures . Following MHV-A59 infection in vitro, approximately 10% of oligodendrocytes and 30% of astrocytes expressed viral antigens in the absence of overt cytopathic effect . All cultures released infectious virus for the lifetime of the cultures, for at least 45 days in the case of mixed glial cultures . Cultures derived from previously infected mice were similar to those infected in vitro with respect to percentage of cells expressing viral antigen and levels of infectious virus produced . These results show (1) that glial cells are early sites of infection in vivo as well as sites of infection in in vitro cultures, and (2) that glial cells support a non-lytic but productive infection in vitro and thus may contribute to viral persistence in vivo .

SOLUTION:
Coronavirus mouse hepatitis virus (MHV)-A59 causes a persistent, productive infection in primary glial cell cultures