Nucleic acids represent a promising platform for creating vaccines. One disadvantage of this approach is its relatively low immunogenicity. Electroporation (EP) is an effective way to increase the DNA vaccines immunogenicity. However, due to the different configurations of devices used for EP, EP protocols optimization is required not only to enhance immunogenicity, but also to ensure greater safety and tolerability of the EP procedure.

AREA COVERED:

An data analysis for recent years on the DNA vaccines delivery against viral and parasitic infections using EP was carried out. The study of various EP physical characteristics, such as frequency, pulse duration, pulse interval, should be considered along with the immunogenic construct design and the site of delivery of the vaccine, through the study of the immunogenic and protective characteristics of the latter.

EXPERT OPINION:

Future research should focus on regulating the humoral and cellular response required for protection against infectious agents by modifying the EP protocol. Significant efforts will be directed to establishing the possibility of redirecting the immune response toward the Th1 or Th2 response by changing the EP physical parameters. It will allow for an individual selective approach during EP, depending on the pathogen type of an infectious disease.

2024-09-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

(+)-fenchol and (−)-isopinocampheol derivatives targeting the entry process of filoviruses

Article

作者: Sokolova, Anastasiya S ; Rogachev, Artem D ; Tolstikova, Tatyana G ; Yarovaya, Olga I ; Volkova, Natalia V ; Okhina, Alina A ; Nikitina, Tatiana V ; Baev, Dmitriy S ; Mordvinova, Ekaterina D ; Salakhutdinov, Nariman F ; Chvileva, Anastasiya S ; Shcherbakov, Dmitriy N ; Shnaider, Tatiana A

The increasing frequency of filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (-)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent antiviral compounds, with half-maximal inhibitory concentration (IC₅₀) 1.4-20 μМ against Lenti-EboV-GP infection and 11.3-47 μМ against Lenti-MarV-GP infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the antiviral activity may be due to dual effects. This study offers new antiviral agents that are worthy of further exploration.

2024-05-16·Frontiers in Bioscience-Landmark

Catalase Activity of IgG and κκ-IgG, λλ-IgG, and κλ-IgG Subfractions in HIV-Infected Patients and Healthy Donors

Article

作者: Gashnikova, Natalya M ; Timofeeva, Anna M ; Sedykh, Sergey E ; Tolmacheva, Anna S ; Maksimenko, Lada V ; Nevinsky, Georgy A ; Onvumere, Margarita K

BACKGROUND:

Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth of evidence suggests that, along with canonical enzymes of reactive oxygen species regulation, human blood contains antibodies with peroxidase, superoxide dismutase, and catalase activities. Here we show that the catalase activity of IgGs and their κκ-IgG, λλ-IgG, and κλ-IgG subfractions of HIV-infected individuals is significantly different compared to the healthy donors.

METHODS:

Protein G-Sepharose sorbent was used to resolve IgG from blood of healthy donors and HIV-infected patients by affinity chromatography. Subfractions of κκ-IgG, λλ-IgG, and κλ-IgG were separated from IgGs samples of each group by affinity chromatography on sorbents containing immobilized antibodies to κ or λ light human chains. The IgG catalase activity level was measured spectrophotometrically by evaluating the decrease in optical density (A240) due to hydrogen peroxide decomposition.

RESULTS:

The relative catalase activity of antibodies from HIV-infected patients (kcat = (1.41 ± 0.92) × 103 min-1, 95% CI: [1.01-1.81]) was statistically significant, 1.6 times higher (p = 0.014) compared to apparently healthy donors ((0.86 ± 0.49) × 103, 95% CI: [0.69-1.03]). The activity level of κκ-IgG HIV-infected patients ((0.44 ± 0.04) × 103 min-1) was 1.4 times higher than that of λλ-IgGs ((0.31 ± 0.025) × 103 min-1); the opposite was observed for κκ-IgGs from apparently healthy donors, which activity ((0.17 ± 0.015) × 103 min-1) was 3.1 times lower compared to λλ-IgGs ((0.53 ± 0.045) × 103 min-1).

CONCLUSIONS:

Thus, the data obtained may indicate that IgG with increased catalase activity may prevent harmful processes arising from oxidative stress in HIV-infected patients, acting as an additional natural molecular mechanism of regulation of hydrogen peroxide level.

项与 State Research Center of Virology and Biotechnology VECTOR 相关的新闻（医药）

2022-10-31

·PRNewswire

Avirmax CMC Inc. Received License for cGMP Gene Therapy Vector Production by the California Department of Public Health

HAYWARD, Calif., Oct. 31, 2022 /PRNewswire/ -- Avirmax CMC Inc., a global leader in recombinant adeno associate virus vector (rAAV) innovation and manufacturing process development, using a recombinant baculovirus Sf9 (rBV-Sf9-AAV) system, has completed its brand-new facility in Hayward, CA (San Francisco Bay Area). The facility has received cGMP license approval by the California Department of Public Health (CDPH)-Food & Drug Branch, for the production of rAAV drug products for use in clinical investigations. Continue Reading The new 20,000 sq.ft. state-of-the-art manufacturing facility is composed of three functional areas – developmental laboratories, testing laboratories and cGMP production suites consisting of B, C, and D clean room classifications, which are prepared for rAAV Contract Research, Development, Manufacturing Organization (CDMO) service. The new cGMP facility will support us to deliver high yield and quality vectors efficiently, timely and cost effectively Tweet this This facility will produce rAAV using single use bioreactors (SUB) in an animal free, serum free suspension culture system with yields of 1016-17 vector genome (vg) per batch with a production window of about two months. Production scales at 50L, 200L and 1000L, are available to customers depending on their clinical trial size and dose requirements. The company has a worldwide exclusive license from ViroVek Inc. enabling cGMP production of AAV gene therapeutics using the Bac-to-AAV technology, which utilizes an engineered artificial intron consisting of an insect promoter in both the AAV rep and cap sequences, coupled with a versatile baculovirus expression system. The suspension insect culture system dramatically enhances the stability of recombinant baculoviruses, the infectivity of the AAV vectors, and AAV production yield, capable of reaching as high as 1e+15 vg/L. The Sf9 cell culture provides higher pathogen safety assurance for gene therapy products than those manufactured using human or other mammalian cell culture systems (i.e., HEK293 or HeLa-3 cells) since the Sf9 cell culture hardly supports mammalian virus propagation. The Sf9 manufacturing platform can be operated under a BSL-1 biological safety environment, as used in the production of the recombinant proteins (i.e., monoclonal antibodies) by Chinese hamster ovarian (CHO), baby hamster kidney (BHK) cells. "Our team has extensive experience and knowledge in recombinant AAV technology development and in rAAV manufacturing. With our new facility, Avirmax CMC Inc. is able to deliver high yield and quality vectors efficiently, timely and cost effectively. Avirmax CMC Inc. is committed to continuously innovate and develop technologies in collaborative relationships with our customers and to solve challenges in rAAV vector process development and manufacturing," commented Shengjiang (Shawn) Liu, Ph.D., DVM, President & CEO of the company. With the recent CDPH approval of the cGMP facility, and by applying their expertise and manufacturing experience accumulated in the past years, the company is capable of supporting clients with integrated solutions, from DNA to rAAV drug product (DP), including rAAV vector design, molecular cloning, expression cassette optimization, process development, manufacturing, comprehensive vector analysis and characterization, as well as with the regulatory strategy for gene therapy products. About Avirmax CMC, Inc. Avirmax CMC, Inc., a spin-off of Avirmax Inc., based in the San Francisco Bay Area, is dedicated to the development and manufacture of rAAV vector mediated biotherapeutics using its proprietary protein therapeutics and Bac-to-AAV technologies. The company was founded by seasoned entrepreneur Shengjiang (Shawn) Liu, Ph.D., DVM, who is a veteran in biologics including rAAV based drug development. Dr. Liu was the group leader of Genentech's Research Virology Lab, co-founder and president of Abmaxis Inc. and Chief Scientist at Bayer Pharmaceuticals. The company's co-founder, Haifeng Chen, PhD., was founder & CEO of ViroVek Inc. Dr. Chen is a pioneer in the Bac-to-AAV system that was developed for the large-scale production of rAAV vectors. Avirmax CMC Inc. is dedicated to offer its clients with great transparency, flexibility and process expertise, superior high quality and titer AAV vectors, manufacturing capacity and regulatory strategy know-how. For more information, please visit at . Contact Please contact June Song, Manager for Executive Administration Email: [email protected] Tel: +1-510-641-0201 Address 25503 Whitesell Street Hayward 94545 CA USA SOURCE Avirmax

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