It has been 20 years since Newcastle disease virus (NDV) was first used as a vector. The past two decades have witnessed remarkable progress in vaccine generation based on the NDV vector and optimization of the vector. Protective antigens of a variety of pathogens have been expressed in the NDV vector to generate novel vaccines for animals and humans, highlighting a great potential of NDV as a vaccine vector. More importantly, the research work also unveils a major problem restraining the NDV vector vaccines in poultry, i.e., the interference from maternally derived antibody (MDA). Although many efforts have been taken to overcome MDA interference, a lack of understanding of the mechanism of vaccination inhibition by MDA in poultry still hinders vaccine improvement. In this review, we outline the history of NDV as a vaccine vector by highlighting some milestones. The recent advances in the development of NDV-vectored vaccines or therapeutics for animals and humans are discussed. Particularly, we focus on the mechanisms and hypotheses of vaccination inhibition by MDA and the efforts to circumvent MDA interference with the NDV vector vaccines. Perspectives to fill the gap of understanding concerning the mechanism of MDA interference in poultry and to improve the NDV vector vaccines are also proposed.

As tumor-associated antigens are not well characterized for the majority of human tumors, polyvalent vaccines prepared with whole-tumor antigens are an attractive approach for tumor vaccination. Vascular endothelial growth factor receptor-2 (VEGFR2), as a model antigen with which to explore the feasibility of immunotherapy, has shown great promise as a tumor vaccine. However, the efficacy of immunotherapy is often not ideal when used alone. In this study, we explored the therapeutic efficacy of an irradiated AdVEGFR2-infected cell vaccine-based immunotherapy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model. An adenovirus encoding the VEGFR2 gene (AdVEGFR2) was constructed. Lethally irradiated, virus-infected 4T1 cells were used as vaccines. Vaccination with lethally irradiated AdVEGFR2-infected 4T1 cells inhibited subsequent tumor growth and pulmonary metastasis compared with challenge inoculations. Angiogenesis was inhibited, and the number of CD8+ T lymphocytes was increased within the tumors. Antitumor activity was also caused by the adoptive transfer of isolated spleen lymphocytes. In vitro, the expression of HMGB1 and HSP70 in the AdVEGFR2‑infected 4T1 cells was increased, and was involved in the activation of tumor antigen-specific T-cell immunity. Our results indicate that the immunotherapy based on irradiated AdVEGFR2-infected whole-cancer cell vaccines may be a potentially effective strategy for 4T1 cancer treatment.

Small non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5′ untranslated region (5′ UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.

Background Small non-coding RNAs (sRNAs) regulate bacterial gene expression at the post-transcriptional level. STnc640 is a type of sRNA that was identified in Salmonella Typhimurium. Results In this study, STnc640 in Salmonella Enteritidis was confirmed to be an Hfq-dependent sRNA. TargetRNA software analysis showed that fimbrial genes fimA and bcfA were likely to be the target genes of STnc640. To investigate the target mRNAs and function of STnc640 in pathogenicity, we constructed the deletion mutant strain 50336△ stnc640 and the complemented strain 50336△ stnc640 /p stnc640 in Salmonella Enteritidis 50336. The RT-qPCR results showed that the mRNA level of fimA was decreased, while bcfA was unchanged in 50336△ stnc640 compared with that in the wild type (WT) strain. The adhesion ability of 50336△ stnc640 to Caco-2 cells was increased compared to the 50336 WT strain. The virulence of 50336△ stnc640 was enhanced in a one-day-old chicken model of S. Enteritidis disease as determined by quantifying the 50% lethal dose (LD 50 ) of the bacterial strains. Conclusions The results demonstrate that STnc640 contributes to the virulence of Salmonella Enteritidis.

A recent study suggests that ribosome MARylation in cancers maintains proteostasis by reducing protein synthesis and preventing toxic protein aggregation. Mechanistically, NMNAT-2 is a cytosolic NAD + synthase that supports the catalytic activity of PARP-16, which mediates ribosomal proteins MARylation. Ribosomal protein MARylation regulates polysomes assembly or function through the 3′-untranslated region (3′-UTR) stem-loop secondary structures in mRNAs, resulting in reduced protein synthesis and preventing toxic protein aggregation, thus supporting the growth of cancer cells during accelerated cell growth. When PARP-16 or NMNAT-2 is deleted, the stem-loop element in the 3′-UTRs of mRNAs increases polysome loading, enhances protein synthesis, promotes toxic protein aggregation, leading to inhibited cancer cell growth. Collectively, ribosome MARylation provides us with an exciting and scientific direction for us to understand cancers.