Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study.

Microvascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.

Non-neutralizing Antibodies Directed at Conservative Influenza Antigens.

At the moment, developing new broad-spectrum influenza vaccines which would help avoid annual changes in a vaccine's strain set is urgency. In addition, developing new vaccines based on highly conserved influenza virus proteins could allow us to better prepare for potential pandemics and significantly reduce the damage they cause. Evaluation of the humoral response to vaccine administration is a key aspect of the characterization of the effectiveness of influenza vaccines. In the development of new broad-spectrum influenza vaccines, it is important to study the mechanisms of action of various antibodies, including non-neutralizing ones, as well as to be in the possession of methods for quantifying these antibodies after immunization with new vaccines against influenza. In this review, we focused on the mechanisms of anti-influenza action of non-neutralizing antibodies, such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and antibody-mediated complement-dependent cytotoxicity (CDC). The influenza virus antigens that trigger these reactions are hemagglutinin (HA) and neuraminidase (NA), as well as highly conserved antigens, such as M2 (ion channel), M1 (matrix protein), and NP (nucleoprotein). In addition, the mechanisms of action and methods for detecting antibodies to neuraminidase (NA) and to the stem domain of hemagglutinin (HA) of the influenza virus are considered.

[Construction of recombinant adenoviral vector expressing genes of the conservative influenza proteins M2 and nucleoprotein].

Influenza is a highly contagious and one of the most massive infection diseases. General epidemiological significance has a strain, which belongs to subtype A. A high degree of genetic variety leads to the permanent changes in the antigenic structure of the influenza virus. Therefore, the current influenza vaccines require periodic updating of the composition of strains. Presently, it is important to develop a universal vaccine that can protect against different strains of influenza A virus at the same time and is based on the conserved antigens of the influenza virus. The recombinant adenovirus vectors expressing genes of conserved viral antigenes may be a promising candidate vaccine against influenza A. Using the method of the homologous recombination, we developed in this study recombinant adenovirus of fifth serotype that expresses genes of the ion channel M2 and nucleoprotein NP of the influenza virus A. Genes of the consensus protein M2 and NP of human influenza A virus were included into the structure of the viral genome. The expression of the antigens M2 and NP using recombinant adenovirus vector was detected by a Western blot assay. The immunogenicity of the developed recombinant adenovirus vector was demonstrated by the intranasal immunization of laboratory mice.

Recombinant influenza vaccines.

This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery platform for a variety of genetic vaccines. Adenoviruses can efficiently penetrate the human organism through mucosal epithelium, thus providing long-term antigen persistence and induction of the innate immune response. This review provides an overview of the practicability of the production of new recombinant influenza cross-protective vaccines on the basis of adenoviral vectors expressing hemagglutinin genes of different influenza strains.

[Protective properties of candidate genetically engineered vaccines against avian influenza viruses constructed on the basis of recombinant adenoviral vectors].

AIM: To design and study the properties of candidate vaccines against avian influenza based on recombinant adenoviral vectors expressing H5 hemagglutinin. MATERIALS AND METHODS: Recombinant adenoviral vectors were constructed as described in "Stratagene" (Ad Easy Adenoviral Vector System). For immunization of animals, recombinant candidate vaccines were administered intranasally twice. Titer of hemagglutinating antibodies were measured by hemaglutination inhibition assay. RESULTS: It was demonstrated that administration of vaccines to animals completely protects them from a lethal dose challenge with H5N2 influenza virus. Protective effect of vaccines remained for 6 months after immunization. Additionally, highly effective cross-protection of the immunized animals against heterologous strain of H5 influenza virus was demonstrated. CONCLUSION: Obtained results show good prospects for usage of recombinant adenoviral vectors as a basis for development of new generation effective vaccines against influenza.

Induction of a Protective Heterosubtypic Immune Response Against the Influenza Virus by using Recombinant Adenoviral Vectors Expressing Hemagglutinin of the Influenza H5 Virus.

Influenza viruses are characterized by a high degree of antigenic variability, which causes the annual emergence of flu epidemics and irregularly timed pandemics caused by viruses with new antigenic and biological traits. Novel approaches to vaccination can help circumvent this problem. One of these new methods incorporates genetic vaccines based on adenoviral vectors. Recombinant adenoviral vectors which contain hemagglutinin-encoding genes from avian H5N1 and H5N2 (Ad-HA5-1 and Ad-HA5-2) influenza viruses were obtained using the AdEasy Adenoviral Vector System (Stratagene). Laboratory mice received a double intranasal vaccination with Ad-HA5-1 and Ad-HA5-2. This study demonstrates that immunization with recombinant adenoviruses bearing the Н 5 influenza virus hemagglutinin gene induces a immune response which protects immunized mice from a lethal dose of the H5 influenza virus. Moreover, it also protects the host from a lethal dose of the H1 virus, which belongs to the same clade as H5, but does not confer protection from the subtype H3 influenza virus, which belongs to a different clade.

Gene therapy of amyotrophic lateral sclerosis.

Two-year experiments were performed to evaluate the neurotrophic effect of hypoxia-inducible factors (vascular endothelial growth factor and angiogenin) expressed in recombinant human adenoviruses in amyotrophic lateral sclerosis. Randomized placebo-controlled trial demonstrated safety and good tolerability of the recombinant antiviral drugs. The life span of patients under conditions of hypoxia increased after treatment with the test drug, which was probably related to improved resistance of motoneurons. The presence of virus-neutralizing antibodies decreases the effectiveness of adenoviral vectors, which necessitates differential approach to the selection of patients and continuous monitoring of gene therapy.