Candidate Vectors Research Articles

Fast data selection for SVM training using ensemble margin

Support Vector Machine (SVM) is a powerful classification method. However, it suffers a major drawback: the high memory and time complexity of the training which constrains the application of SVM to large size classification tasks. To accelerate the SVM training, a new ensemble margin-based data selection approach is proposed. It relies on a simple and efficient heuristic to provide support vector candidates: selecting lowest margin instances. This technique significantly reduces the SVM training task complexity while maintaining the accuracy of the SVM classification. A fast alternative of our approach we called SVIS (Small Votes Instance Selection) with great potential for large data problem is also introduced.

Isolation and characterization of Babesia pecorum sp. nov. from farmed red deer (Cervus elaphus).

The diversity of Babesia species infecting cervids in parts of central and southern Spain was analyzed by collecting blood from farmed red deer (Cervus elaphus). Babesia sp. was isolated in vitro from two red deer herds in Cádiz and Ciudad Real. The number of Babesia sp. carriers differed between the two herds: 36/77 in Cádiz and 1/35 in Ciudad Real. Hyalomma lusitanicum was the most prevalent tick species identified on the Cádiz farm vegetation and on sampled animals, and is therefore a candidate vector. The molecular characteristics of 21 isolates were determined by complete (8 isolates) or partial (13 isolates) 18S rRNA gene sequencing. The sequences were highly similar (over 99.4% identity) and 6 sequence types were identified at the level of one herd only, demonstrating a rather high genetic diversity. They formed a monophyletic clade, and members of the three main sequence types shared a similar morphology and the same erythrocyte susceptibility pattern. This clade also included Babesia sp. Xinjiang isolated from sheep in China and Babesia sp. identified in giraffe in South Africa, with identities higher than 98.3% and statistically relevant phylogenetic support. None of the biological properties analyzed for both Babesia from red deer and Babesia sp. Xinjiang allowed their differentiation (ability to develop in vitro in erythrocytes from cattle and sheep, as well as in erythrocytes from different cervids, unsuccessful infection of calves). We propose the Babesia isolated from red deer as a new species named B. pecorum. Whether Babesia sp. Xinjiang and the Babesia characterized in South Africa belong to the same species is debated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0078-7) contains supplementary material, which is available to authorized users.

Recombinant Mycobacterium bovis bacillus Calmette-Guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques.

Live attenuated nonpathogenic Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gag expression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in an in vitro screen for augmented immunogenicity. We demonstrated that BCG-SIVgag is able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for >1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.

Polycationic star polymers with hyperbranched cores for gene delivery

Core-shell type stars synthesized via atom transfer radical polymerization were used for the delivery of nucleic acids. The interior of the stars consisted of hyperbranched poly(arylene oxindole), while the arms were composed of poly(N,N-dimethylaminoethyl methacrylate). The length of the star arms varied in degree of polymerization (DP) from 14 to 98. The hydrodynamic radius of the structures measured in water indicated the presence of small aggregates, while isolated stars ranging in size from 14 to 29 nm were seen in organic solvent. The phase transition temperatures of the stars in water, measured in basic conditions, were shifted to lower values with increasing DP of the arms. Stable polyplexes of stars with plasmid DNA were formed. Their size varied from 300 nm to 400 nm, depending upon the DP of arms. The zeta potential of the polyplexes was positive, which facilitated their cellular uptake. The DP of the arms influenced the transfection efficiency of HT-1080 cells, demonstrating that stars are promising candidates for synthetic gene vectors.

Egg parasitoids (Hymenoptera: Mymaridae and Trichogrammatidae) of Kolla paulula (Walker) (Hemiptera: Cicadellidae) in Taiwan

Pseudoligosita nephotetticum (Mani) (Hymenoptera: Trichogrammatidae) and Gonatocerus (Cosmocomoidea) sp. (Hymenoptera: Mymaridae) have been identified for the first time as egg parasitoids of the sharpshooter leafhopper Kolla paulula (Walker) (Hemiptera: Cicadellidae: Cicadellinae: Cicadellini) in Taiwan. K. paulula has been recently identified as a candidate vector of the phytopathogenic bacterium Xylella fastidiosa, the causative agent of Pierce's disease of grapes and similar diseases of other affected plants in Taiwan, and thus has become of particular economic importance. Also provided is a summary of the known records of egg parasitoids (Mymaridae and Trichogrammatidae) of other leafhoppers from the tribe Cicadellini in the world, as well as taxonomic notes on P. nephotetticum.

Depth-Assisted Temporal Error Concealment for Intra Frame Slices in 3-D Video

We propose a depth-assisted error concealment method for slice losses in intra frames of 2-D+depth encoded 3-D video. Intra frames in the depth sequence are offset from intra frames in the 2-D view sequence, such that the corresponding frames in the other sequence are not also intra mode. For slice losses in an intra frame of the 2-D sequence, motion vector (MV) candidates to conceal the lost macroblocks come from the co-located MVs in the depth frame as well as from MVs in the previous 2-D frame chosen based on motion information from the depth frame. Then the temporal smoothness of the depth sequence is used to filter out MV candidates. Finally, an enhanced distortion criterion is used for MV selection, based on contour information in the depth frame and boundary matching. Experimental results show that the proposed method provides improved performance over existing methods.

Rickettsia raoultii, the predominant Rickettsia found in Dermacentor silvarum ticks in China–Russia border areas

Since the year 2000, clinical patterns resembling tick-borne rickettsioses have been noticed in China-Russia border areas. Epidemiological data regarding species of the aetiological agent, tick vector prevalence and distribution as well as incidence of human cases in the areas are still sparse to date. In order to identify Rickettsia species occurring in the areas, we investigated Dermacentor silvarum collected in the selected areas. Rickettsia raoultii was the predominant Rickettsia found in D. silvarum evident with ompA, ompB, gltA and 17 kDa protein genes. The Rickettsia prevalence in D. silvarum appeared to be 32.25 % with no sex difference. The results extend the common knowledge about the geographic distribution of R. raoultii and its candidate vector tick species, which suggest an emerged potential threat of human health in the areas.

Novel influenza virus vectors expressing Brucella L7/L12 or Omp16 proteins in cattle induced a strong T-cell immune response, as well as high protectiveness against B. abortus infection

This paper presents the results of a study of the immunogenicity and protectiveness of new candidate vector vaccine against Brucella abortus – a bivalent vaccine formulation consisting of a mixture of recombinant influenza A subtype H5N1 or H1N1 (viral constructs vaccine formulation) viruses expressing Brucella ribosomal protein L7/L12 and Omp16, in cattle. To increase the effectiveness of the candidate vaccine, adjuvants such as Montanide Gel01 or chitosan were included in its composition. Immunization of cattle (heifers aged 1–1.5 years, 5 animals per group) with the viral constructs vaccine formulation only, or its combination with adjuvants Montanide Gel01 or chitosan, was conducted via the conjunctival method using cross prime (influenza virus subtype H5N1) and booster (influenza virus subtype H1N1) vaccination schedules at an interval of 28 days. Vaccine candidates were evaluated in comparison with the positive (B. abortus S19) and negative (PBS) controls. The viral constructs vaccine formulations, particularly in combination with Montanide Gel01 adjuvant promoted formation of IgG antibodies (with a predominance of antibodies of isotype IgG2a) against Brucella L7/L12 and Omp16 proteins in ELISA. Moreover, these vaccines in cattle induced a strong antigen-specific T-cell immune response, as indicated by a high number of CD4+ and CD8+ cells, as well as the concentration of IFN-γ, and most importantly provided a high level of protectiveness comparable to the commercial B. abortus S19 vaccine and superior to the B. abortus S19 vaccine in combination with Montanide Gel01 adjuvant. Based on these findings, we recommended the bivalent vaccine formulation containing the adjuvant Montanide Gel01 for practical use in cattle.

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Human antimicrobial peptides are of interest for the development of positron emission tomography (PET) tracers as they exhibit desirable characteristics that make them good candidates for targeting vectors. Due to their natural role in the innate immune system they selectively bind to pathogenic bacteria and yeast, whilst remaining minimally immunogenic and cytotoxic to humans. Research into ubiquicidin (UBI)-based tracers has focused on (99m)Tc as a radionuclide, however, the use of bi-functional chelators such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), in combination with ⁶⁸Ga as a radionuclide, allows for a simple radiolabeling procedure which is preferable in a clinical setting using PET/CT. The peptides fragments UBI29-41, UBI30-41 were synthesized by standard microwave Fmoc/tert-butyl (tBu)-solid phase synthetic protocols. Characterizations were performed using analytical HPLC and LC/MS. Both NOTA-conjugated peptides were exposed to (nat)Ga³⁺; their complexed form was quantified by direct LC/MS injection. This complexation was utilized to testify bacterial and mammalian cell binding potential of fluorophore-linked NOTA-UBI29-41/30-41. ⁶⁸Ga labeled NOTA-UBI fragments were also tested for competitive interaction to Staphylococcus aureus to proof the binding target. ⁶⁸Ga was eluted from SnO₂- and TiO₂-based ⁶⁸Ge/⁶⁸Ga generators using fractionated elution and anion exchanged-based post-procession. NOTA-peptide radiolabeling was carried out including optimization of buffer molarity, NOTA-peptide concentration(s), incubation temperature and -duration as well as considering various SPE purification cartridges. Pure UBI29-41, UBI30-41 and NOTA-UBI30-41 were successfully characterized. Both, NOTA-UBI fragments exhibited complexation rates to (nat)Ga³⁺)≥ 99%. The percentage binding was significantly higher to Staphylococcus aureus bacilli over Mt4 human leucocytes (P>0.05) for NOTA-UBI29-41[Lys(Abz)]<NOTA-UBI30-41[Lys(Abz)]. Significant lower binding was observed for both ⁶⁸Ga-labeled NOTA-UBI fragments (P >0.03) after pre-incubation with excess unlabeled NOTA-UBI. Reproducible ⁶⁸Ga radiolabeling ranged for 51-85% and 46-78% for NOTA-UBI29-41 and NOTA-UBI30-41, respectively. Aside from successful peptide syntheses the first ever ⁶⁸Ga-radiolabeling method is reported for NOTA-UBI fragments. The NOTA-conjugation didn't compromise the selective and specific interaction with bacterial cells in vitro. Both tracers are warranting prospective imaging of infection with PET/CT.

Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells

Attenuated Listeria monocytogenes (LM) is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex (MHC)-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain ΔdalΔdat (Lmdd) to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma (HCC). After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon (IFN)-γ-producing CD8(+) T cells and IFN-γ secretion. Lmdd-CD24 also enhanced the number of IL-4- and IL-10-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1-6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell (Treg) numbers and an enhancement of specific CD8(+) T-cell activity were observed in the tumor-infiltrating lymphocytes (TILs). These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.

Next Generation Sequencing Reveals Regulation of Distinct Aedes microRNAs during Chikungunya Virus Development

BackgroundApplication of genomics and Next Generation sequencing has led to the identification of new class of cellular functional molecules, namely, small RNAs. Of the several classes of ncRNAs (non-coding RNA), microRNAs have been demonstrated to exert determinative influence on various cellular processes. It is becoming abundantly clear that host/vector/pathogen encoded microRNAs impact eventual pathogenesis. In this context, the participation of vector based microRNAs in disease transmission and pathogen development is being investigated intensively. A few studies have highlighted the role of vector encoded microRNAs in pathogen infection. We conducted this study to evaluate the role of host miRNAs upon CHIKV (Chikungunya Virus) infection in an important vector, Aedes albopictus.FindingsWe identified 88 and 79 known miRNAs in uninfected and CHIKV infected Ae. albopictus Singh's cell line respectively. We further identified nine novel miRNAs in Ae. albopictus. Comparison of the two libraries revealed differential expression of 77 common miRNAs between them. CHIKV infection specifically altered the miRNA profile of a specific set of eight miRNAs. Putative targets of these regulated miRNAs were identified and classified into their pathways.ConclusionsIn our study we have identified and described the profiles of various miRNAs upon CHIKV infection in Ae. albopictus. This investigation provides an insight about cellular modification by miRNAs during CHIKV infection and the results provide leads for identifying potential candidates for vector based antiviral strategies.

Isolation and characterization of

The diversity of Babesia species infecting cervids in parts of central and southern Spain was analyzed by collecting blood from farmed red deer (Cervus elaphus). Babesia sp. was isolated in vitro from two red deer herds in Cádiz and Ciudad Real. The number of Babesia sp. carriers differed between the two herds: 36/77 in Cádiz and 1/35 in Ciudad Real. Hyalomma lusitanicum was the most prevalent tick species identified on the Cádiz farm vegetation and on sampled animals, and is therefore a candidate vector. The molecular characteristics of 21 isolates were determined by complete (8 isolates) or partial (13 isolates) 18S rRNA gene sequencing. The sequences were highly similar (over 99.4% identity) and 6 sequence types were identified at the level of one herd only, demonstrating a rather high genetic diversity. They formed a monophyletic clade, and members of the three main sequence types shared a similar morphology and the same erythrocyte susceptibility pattern. This clade also included Babesia sp. Xinjiang isolated from sheep in China and Babesia sp. identified in giraffe in South Africa, with identities higher than 98.3% and statistically relevant phylogenetic support. None of the biological properties analyzed for both Babesia from red deer and Babesia sp. Xinjiang allowed their differentiation (ability to develop in vitro in erythrocytes from cattle and sheep, as well as in erythrocytes from different cervids, unsuccessful infection of calves). We propose the Babesia isolated from red deer as a new species named B. pecorum. Whether Babesia sp. Xinjiang and the Babesia characterized in South Africa belong to the same species is debated.

Design and Production of mRNA-based Gene Vectors for Therapeutic Reprogramming of Cell Fate

Recent advances in therapeutically important cell fate reprogramming fuelled a renaissance in the use of mRNAbased gene vectors. Thus, mRNA vectors were successfully employed to induce lasting epigenetic changes in various target cells making them short-listed vector candidates for the manufacture of therapeutic engraftment materials for autologous transplantation, artificial human tissues for drug discovery via high-throughput screening projects and also for therapeutic cell trans-differentiation directly in the human body. De-differentiation of cells into ‘induced pluripotent stem cells’, transgene-directed differentiation and trans-differentiation require the simultaneous delivery of a number of regulatory factors, and, favourably, potent reprogramming vector cocktails can be straightforwardly assembled from a selection of mRNA species. In addition, several proteins can be conveniently expressed from a single mRNA using internal ribosome entry sites (IRESes) or, alternatively, fusion proteins supplemented with ‘polypeptide-cleaving’ ribosome skipping sequences. This review is focused on the design and production of cell-fate changing mRNAs.

Vector competence of the tick Ixodes sinensis (Acari: Ixodidae) for Rickettsia monacensis

Cases of Mediterranean Spotted Fever like rickettsioses, caused by Rickettsia monacensis, have become more common in the last 10 years. In China, natural infection of R. monacensis in various tick species has been confirmed but the vector(s) of R. monacensis have not been recorded. The prevalence of R. monacensis in >1500 Ixodidae ticks from central and southern China was determined using centrifugation-shell vial culture and polymerase chain reaction techniques. The predominant species, Ixodes sinensis, harbored a natural infection of R. monacensis and was assumed to be a vector candidate of R. monacensis. Experimental transmissions were initialized by infecting Rickettsia-free tick colonies with R. monacensis using capillary tube feeding (CTF) or immersion techniques. Transstadial and transovarial transmissions, and transmission from ticks to mice, were conducted under laboratory conditions. R. monacensis was isolated and identified from hemolymph of Ixodes sinensis using molecular techniques. Transovarial transmission of R. monacensis from infected ♀I. sinensis to offspring was documented and infected offspring successfully passed Rickettsia to mice. Transstadial transmission rates were 58% in larva to nymph and 56% in nymph to adult stages. Infected nymphs and adults were also able to infect mice. I. sinensis is a competence vector for R. monacensis as demonstrated by natural infection and transmission studies.

Improvements in closest point search based on dual HKZ-bases

In this paper we review the technique to solve the CVP based on dual HKZ-bases by J. Blömer [4]. The technique is based on the transference theorems given by Banaszczyk [3] which imply some necessary conditions on the coefficients of the closest vectors with respect to a basis whose dual is HKZ-reduced. Recursively, starting with the last coefficient, intervals of length i can be derived for the i-th coefficient of any closest vector. This leads to n! candidates for closest vectors. In this paper we refine the necessary conditions derived from the transference theorems, giving an exponential reduction of the number of candidates. The improvement is due to the fact that the lengths of the intervals are not independent. In the original algorithm the candidates for a coefficient pair (vi,vi+1) correspond to the integer points in a rectangle of volume i⋅(i+1). In our analysis we show that the candidates for (vi,vi+1) in fact lie in an ellipse with transverse and conjugate diameter i+1, respectively i. This reduces the expected number of points to be enumerated by an exponential factor of about 0.886n. We further show how a choice of the coefficients (vn,…,vi+1) influences the interval from which vi can be chosen. Numerical computations show that these considerations allow to bound the expected number of points to be enumerated by n0.75n for 10⩽n⩽2000. Under the assumption that the Gaussian heuristic for the length of the shortest nonzero vector in a lattice is tight, this number can even be bounded by 122nnn/2.

The Origin and Evolution of Six Miniature Inverted-Repeat Transposable Elements in Bombyx mori and Rhodnius prolixus

Miniature inverted-repeat transposable elements (MITEs) are a specific group of nonautonomous DNA transposons, and they are distributed in a wide range of hosts. However, the origin and evolutionary history of MITEs in eukaryotic genomes remain unclear. In this study, six MITEs were identified in the silkworm (Bombyx mori). Five elements are grouped into four known superfamilies of DNA transposons, and one represents a novel class of MITEs. Unexpectedly, six similar MITEs are also present in the triatomine bug (Rhodnius prolixus) that diverged from the common ancestor with the silkworm about 370 Ma. However, they show different lengths in two species, suggesting that they are different derivatives of progenitor transposons. Three direct progenitor transposons (Sola1, hobo/Ac/Tam [hAT], and Ginger2) are also identified in some other organisms, and several lines of evidence suggested that these autonomous elements might have been independently and horizontally transferred into their hosts. Furthermore, it is speculated that the twisted-wing parasites may be the candidate vectors for these horizontal transfers. The data presented in this study provide some new insights into the origin and evolutionary history of MITEs in the silkworm and triatomine bug.

Novel polyvalent live vaccine against varicella–zoster and mumps virus infections

The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is a highly immunogenic and safe live vaccine that has long been used worldwide. Because its genome is large, making it suitable for inserting foreign genes, vOka is considered a candidate vector for novel polyvalent vaccines. Previously, a recombinant vOka, rvOka-HN, that expresses mumps virus (MuV) hemagglutinin-neuraminidase (HN) was generated by the present team. rvOka-HN induces production of neutralizing antibodies against MuV in guinea pigs. MuV also expresses fusion (F) protein, which is important for inducing neutralizing antibodies, in its viral envelope. To induce a more robust immune response against MuV than that obtained with rvOka-HN, here an rvOka expressing both HN and F (rvOka-HN-F) was generated. However, co-expression of HN and F caused the infected cells to form syncytia, which reduced virus titers. To reduce the amount of cell fusion, an rvOka expressing HN and a mutant F, F(S195Y) were generated. Almost no syncytia formed among the rvOka-HN-F(S195Y)-infected cells and the growth of rvOka-HN-F(S195Y) was similar to that of the original vOka clone. Moreover, replacement of serine 195 with tyrosine had no effect on the immunogenicity of F in mice and guinea pigs. Although obvious augmentation of neutralizing antibody production was not observed after adding F protein to vOka-HN, the anti-F antibodies did have neutralizing activity. These data suggest that F protein contributes to induction of immune protection against MuV. Therefore this recombinant virus is a promising candidate vaccine for polyvalent protection against both VZV and MuV.

Engraftment of a Galactose Receptor Footprint onto Adeno-associated Viral Capsids Improves Transduction Efficiency

New viral strains can be evolved to recognize different host glycans through mutagenesis and experimental adaptation. However, such mutants generally harbor amino acid changes that affect viral binding to a single class of carbohydrate receptors. We describe the rational design and synthesis of novel, chimeric adeno-associated virus (AAV) strains that exploit an orthogonal glycan receptor for transduction. A dual glycan-binding AAV strain was first engineered as proof of concept by grafting a galactose (Gal)-binding footprint from AAV serotype 9 onto the heparan sulfate-binding AAV serotype 2. The resulting chimera, AAV2G9, continues to bind heparin affinity columns but interchangeably exploits Gal and heparan sulfate receptors for infection, as evidenced by competitive inhibition assays with lectins, glycans, and parental AAV strains. Although remaining hepatotropic like AAV2, the AAV2G9 chimera mediates rapid onset and higher transgene expression in mice. Similarly, engraftment of the Gal footprint onto the laboratory-derived strain AAV2i8 yielded an enhanced AAV2i8G9 chimera. This new strain remains liver-detargeted like AAV2i8 while selectively transducing muscle tissues at high efficiency, comparable with AAV9. The AAV2i8G9 chimera is a promising vector candidate for targeted gene therapy of cardiac and musculoskeletal diseases. In addition to demonstrating the modularity of glycan receptor footprints on viral capsids, our approach provides design strategies to expand the AAV vector toolkit.

The prevalence of neutralising antibodies to chimpanzee adenovirus type 6 and type 7 in healthy adult volunteers, patients with chronic hepatitis B and patients with primary hepatocellular carcinoma in China

The presence of neutralising antibodies (NAbs) against adenovirus in the population is a major hurdle preventing the effective use of replication-defective adenoviruses (Ads) as candidates for gene therapy and vaccine vectors for many diseases. Only a few studies have described the epidemiology of pre-existing immunity to chimpanzee Ads in China. To assess the prevalence of NAbs to chimpanzee adenovirus serotypes 6 and 7 (AdC6 and AdC7), we enrolled 998 healthy participants from five regions in China as well as 196 chronic hepatitis B virus (HBV) patients and 193 primary hepatocellular carcinoma (HCC) patients from Chongqing, China. The total seroprevalence rates of AdC6 and AdC7 NAbs in the healthy participants were 12.22% (122/998) (95% confidence interval [CI], 10.34-14.40%) and 13.13% (131/998) (95% CI, 11.17-15.36%), respectively. The seroprevalence rates of AdC6 and AdC7 NAbs in the HBV patients were 21.43% (42/196) (95% CI, 16.26-27.69%) and 25.51% (50/196) (95% CI, 19.92-32.04%), respectively. The seroprevalence rates of AdC6 and AdC7 NAbs in the HCC patients were 27.46% (53/193) (95% CI, 21.65-34.15%) and 31.09% (60/193) (95% CI, 24.98-37.93%), respectively. The seroprevalence rates of these Ads were not associated with age and gender. The present study may provide useful insights for developing future AdC-based vaccines and gene therapies.

Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ

Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.