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.

Example Input: Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels (,2-3-fold) of anti-SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (,10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.
Example Output: A Novel Replication-Competent Vaccinia Vector MVTT Is Superior to MVA for Inducing High Levels of Neutralizing Antibody via Mucosal Vaccination

Example Input: 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.
Example Output: Delivery of steric block morpholino oligomers by (R-X-R) 4 peptides: structure-activity studies

Example Input: In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1α led to viral suppression, indicating that the kinase activity of IRE1α was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1α leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1α is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection. Keywords: endoplasmic reticulum (ER); herpes simplex virus 1 (HSV-1); inositol-requiring enzyme 1 (IRE1); unfolded protein response (UPR); X-box binding protein 1 (XBP1) Viruses 2017, 9, 235 9 of 17 3.3. The Effect of IRE1α Kinase Activity on HSV-1 Replication Next, we investigated the effect of kinase activity of IRE1α on viral replication. IRE1 phosphorylation is generally considered as a reliable indicator of IRE1α kinase activity [45, [49] [50] [51] . Kinase activity of IRE1α was induced at a later stage of viral infection, as indicated by the phosphorylation of IRE1α from 12 h p.i. (Figure 3A ). Viruses 2017, 9, 235 9 of 17 Next, we investigated the effect of kinase activity of IRE1α on viral replication. IRE1 phosphorylation is generally considered as a reliable indicator of IRE1α kinase activity [45, [49] [50] [51] . Kinase activity of IRE1α was induced at a later stage of viral infection, as indicated by the phosphorylation of IRE1α from 12 h p.i. (Figure 3A) . Figure 3. HSV-1 replication is regulated by kinase activity of IRE1α. (A) HSV-1 infection stimulated kinase activity of IRE1α in HEC-1-A cells. HEC-1-A cells were infected with HSV-1 (HF) (moi = 1). Cell lysates were prepared at the times indicated and subject to Western blot analysis using antibodies against total IRE1α, phosphorylated IRE1α, gD-1 and GAPDH; (B) XBP1 splicing induced by APY29 was attenuated by STF-083010 in a dose dependent manner. HEC-1-A cells were treated with both a serial concentration of STF-083010 and 3.125 μM of APY29, and then incubated for 24 h. Total RNA was prepared for measuring the expression of spliced and unspliced XBP1using reverse transcription-PCR analysis; (C,D) Viral replication was inhibited by APY29; (C) Confluent HEC-1-A cells cultured in a 96-well plate were pretreated with serial concentrations of APY29 and then infected with HSV-1 (HF) (moi = 1) for 24 h; (D) Before HEC-1-A cells were infected with HSV-1 (HF) (moi = 1), cells were incubated with both serial concentration of STF-083010 and 3.125 μM of APY29. gD-1 protein expression was determined via In-cell Western, and normalized by DRAQ5 fluorescence at 24 h p.i. Data are mean values ± SD of triplicate determinations (** p < 0.01). Representative results are shown; (E) Inhibition of IRE1α kinase activity had an inhibitory effect on HSV-1 replication in HEC-1-A cells. Cells were presence or absence of APY29 (3.125 μM) or STF-083010 (60 μM) or both of two drugs and then infected with HSV-1 (HF) at moi = 1. Total cellular cells lysates were prepared at 24 h p.i. and subject to Western blot analysis against antibodies to total IRE1α, phosphorylated IRE1α and gD-1; (F) Inactivation of IRE1α kinase activity suppressed HSV-1 replication in Hela cells. Hela cells were transfected with vehicle or IRE1 alpha KA-pcDNA3.EGFP or IRE1 alpha-pcDNA3.EGFP plasmid for 48 h and then infected or mock-infected with HSV-1 (moi = 1). The total and phosphorylated IRE1α,
Example Output:
Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication