Oka Strain Research Articles

‘Synthesis, antiviral activity, molecular docking, and molecular dynamics studies of ethoxy phthalimide pyrazole derivatives against Cytomegalovirus and Varicella-Zoster virus: potential consequences and strategies for developing new antiviral treatments’

Substituted ethoxy phthalimide pyrazole derivatives (6a–e) have been produced using a one-pot synthesis technique. Spectral analysis was used to establish the molecular structure of the synthesized compounds, and they were examined in silico and in vitro for their ability to bind to and inhibit replication of the AD-169 strain, the Davis strain of CMV, the OKA strain and the 07/1 strain of Varicella-Zoster virus (VZV). Molecular Docking was used to estimate the binding mechanism and energy of compounds 4, 6a–e to their respective target proteins, thymidine kinase (TK), Varicella-Zoster protease (VZP) of VZV and tegument protein pp71 (TPpp71) of Cytomegalovirus (CMV). The MIC50 and EC50 were utilized to evaluate the antiviral and cytotoxic activities of test compounds in human embryonic lung (HEL) cells against the two reference medicines, Ganciclovir and Acyclovir. The chemicals studied showed a high affinity for binding sites and near binding sites of target proteins by generating H-bonds, carbon-hydrogen bonds, π-anion, π-sulfur, π-sigma, alkyl and π-alkyl interactions. All of the test compounds (6a–e) had higher binding energy than the standard medications. The ADME/T data suggests that these potential inhibitors are less toxic. Drug-protein complexes are structurally compact and demonstrate minimal conformational change in molecular dynamics (MDs) simulations, indicating stability and stiffness. MM-PBSA and post-simulation analysis can predict lead compound active cavity binding stability. By inhibiting multitargeted proteins, these synthetic compounds may improve antiviral therapy. Our research suggests that these unique synthesized chemicals may be useful and accessible adjuvant antiviral therapy for Varicella Zoster and CMV. Highlights Two components synthesis of substituted ethoxy phthalimide pyrazole derivatives (6a–e). Tested compounds (6a–e) have antiviral and cytotoxicity activity against CMV and Varicella-Zoster virus (VZV) in HEL cells. Compounds bind to TK, Varicella-Zoster protease (VZP) of VZV, and modeled TPpp71 of Cytomegalovirus (CMV). In comparison to reference drugs, compounds have strong binding free energy and interactions with VZV and CMV protein complexes. The RMSD, RMSF, Rg, residual correlative motion (RCM), No. of hydrogen bonds, protein secondary structure content, per-residue protein secondary structure and MM/PBSA energy calculated for the selected compound with thymidine kinase (TK), VZP of VZV, and modeled tegument protein pp71 (TPpp71) of CMV through MD simulation studies for 50 ns. In comparison to the two reference drugs, ligands/compounds were found to meet the Lipinski rule of five and to have strong biological activity. Communicated by Ramaswamy H. Sarma

A booster administration of the OKA/SK strain causes fatal disseminated varicellain an immunocompetent child.

Live varicella vaccines are known to provide robust immunity against varicella zoster virus (VZV) infections. However, problems with viral attenuation have led to pathogenic VZV vaccine strains causing varicella-like rash and herpes zoster in immunocompetent children after immunization. We report the first fatal case of VZV infection caused by OKA/SK strain contained in the vaccine administrated as a booster shot in an immunocompetent child,which has been independently developed from any currently available varicella vaccines that are OKA strain or MAV/06 strain based. The patient died due to sudden pulmonary alveolar hemorrhage as a secondary complication of VZV pneumonitis. Sequencing of the four SNPs unique to the OKA/SK strain (SNP loci 14 035T; 32 626C; 58 777G; 70 319G) enabled discrimination of the strain responsible for the disseminated infection. OKA/SK strain does not have any SNPs in ORF62 postulated to be responsible for the attenuation of varicella vaccines which have been safely and effectively used world-wide or locally, and exclusively enriches a virulent factor in ORF31 identified in parental OKA strain, thus possibly resulting in disseminated VZV infection leading to mortality. Therefore, actions need to be taken to prevent vaccine related morbidity and mortality in children.

Safety of Interchanging the Live Attenuated MAV/06 Strain and OKA Strain Varicella Vaccines in Children.

Two live attenuated varicella vaccine (VZV) strains have been mainly used across the globe: MAV/06 and OKA strains. We aimed to explore the safety of interchanging the two VZV strains for primary and booster immunizations. South Korea's vaccine adverse event reporting system (VAERS) was accessed and searched to find filed reports of all adverse events (AEs) following immunization with the second dose of the varicella vaccine. The electronic medical records were reviewed for all visits to the hospital following the second dose of the varicella vaccine. Of the total 406 study participants, 27.5% (n = 112) were in the MAV/06-MAV/06 group, 30.3% (n = 123) in the MAV/06-OKA, 17.5% (n = 71) in the OKA-MAV/06 group, and 24.6% (n = 100) in the OKA-OKA group. Mean age at immunization with the first dose was 1.10 (standard deviation [SD] ±0.34) years old, and second dose was 4.77 (SD ± 1.13) (p = 0.772 and 0.933, respectively). There were no filed reports of AEs following the second dose in the national VAERS. Hospital visit records showed a total of 10.3% (95% confidence interval [CI], 7.6-13.7) (n = 42) had recorded AEs following the 2nd administered dose; however, only 0.7% (95% CI, 0.2-2.4) (n = 3) were regarded as possibly vaccine related. Two patients in the MAV/06-OKA group were diagnosed with Henoch-Schonlein purpura after the second dose; however, both had also received the MMR vaccine on the same day. No safety signals associated with interchanging the MAV/06 and OKA strain live attenuated varicella vaccines were observed in this patient cohort of healthy children.

Cross-reactive humoral immunity of clade 2 Oka and MAV/06 strain-based varicella vaccines against different clades of varicella–zoster virus

ABSTRACT The currently used Japanese Oka and Korean MAV/06-attenuated varicella vaccine strains belong to clade 2 genotype varicella–zoster viruses (VZV). More than seven clades of VZV exist worldwide. In this study, we investigated the cross-reactivity of antibodies induced by clade 2 genotype vaccines against VZV strains belonging to clades 1, 2, 3, and 5 using a fluorescent antibody to membrane antigen (FAMA) test. Among 59 donors, 29 were vaccinated with the MAV/06 strain MG1111 (GC Biopharma, South Korea) and the other 30 were vaccinated with the Oka strain VARIVAX (Merck, USA). The sera were titrated using FAMA tests prepared with six different VZV strains (two vaccine strains, one wild-type clade 2 strain, and one each of clade 1, 3, and 5 strains). The ranges of geometric mean titers (GMTs) of FAMA against six different strains were 158.7–206.5 and 157.6–238.9 in MG1111 and VARIVAX groups, respectively. GMTs of the MG1111 group against all six strains were similar; however, GMTs of the VARIVAX group showed differences of approximately 1.5-fold depending on the strains. Nevertheless, the GMTs of the two vaccinated groups for the same strain were not significantly different. These results suggest that both MG1111 and VARIVAX vaccinations induce cross-reactive humoral immunity against other clades of VZV.

Disseminated varicella zoster virus infection following live attenuated herpes zoster vaccine: descriptive analysis of reports to Australia’s spontaneous vaccine pharmacovigilance system, 2016–2020

ObjectivesTo examine the reported incidence and features of disseminated varicella zoster virus (VZV) infection following live attenuated herpes zoster vaccine live (ZVL: Zostavax, Merck) in immunocompromised people in Australia.Design and...

Rational Design of a Skin- and Neuro-Attenuated Live Varicella Vaccine: A Review and Future Perspectives.

Primary varicella-zoster virus (VZV) infection causes varicella, which remains a prominent public health concern in children. Current varicella vaccines adopt the live-attenuated Oka strain, vOka, which retains the ability to infect neurons, establish latency and reactivate, leading to vaccine-associated zoster in some vaccinees. Therefore, it is necessary to develop a safer next-generation varicella vaccine to help reduce vaccine hesitancy. This paper reviews the discovery and identification of the skin- and neuro-tropic factor, the open reading frame 7 (ORF7) of VZV, as well as the development of a skin- and neuro-attenuated live varicella vaccine comprising an ORF7-deficient mutant, v7D. This work could provide insights into the research of novel virus vaccines based on functional genomics and reverse genetics.

Immunogenicity and safety profiles of a new MAV/06 strain varicella vaccine in healthy children: A multinational, multicenter, randomized, double-blinded, active-controlled phase III study

Immunization is the most effective preventive strategy against varicella. While the Oka strain is commonly used for varicella vaccination worldwide, Korea widely uses the MAV/06 strain. A new live attenuated MAV/06 strain varicella vaccine (MG1111), which uses the new cell line Medical Research Council-5 for better viral propagation, was developed. MG1111 was approved by Korean health authorities. Here, we report the results of phase III, randomized, double–blind, multicenter study conducted in Korea and Thailand, which compared the immunogenicity and safety profiles of MG1111 versus the control vaccine, VarivaxTM. In total, 515 healthy children (12 month–12 years) were randomized 1:1 to receive either the MG1111 or control vaccine (MG1111: 258, Control: 257). The seroconversion rate (SCR) and geometric mean titer (GMT) were measured using the fluorescent antibody to membrane antigen (FAMA) test. The MG1111 group achieved a SCR of 97.9% (95% CI: 95.2–99.3) after vaccination. The lower limit of 95% CI for SCR difference (MG1111-VarivaxTM) was –4.0%, which was higher than the specified non-inferiority margin of –10%. Further, the GMT of the MG1111 increased from 2.0 to 74.2 (95% CI: 65.0–84.8) and the lower limits of the 95% CI for post–vaccination GMT ratios (MG1111/VarivaxTM) were 0.55 higher than the specified parameter of 0.5. Therefore, the MG1111 group was not statistically inferior to the control vaccine group in terms of SCR and GMT. Furthermore, the MG1111 and control vaccine groups were not significantly different in the percentage of participants showing adverse events—solicited, local, or systemic during 43-day period of observation and serious adverse events during 6 month of observation. The present results indicate that MG1111was not immunologically inferior to VarivaxTM, and safety profiles of MG1111 are similar to those of VarivaxTM.

Evaluation of immunogenicity, safety and breakthrough following administration of live attenuated varicella vaccine in two doses three months apart regimen in Indian children.

Background:In India, where varicella outbreaks are reported at a younger age, a two-dose vaccine schedule administered at an early age could be highly efficacious in preventing varicella infection. The aim of this study was to evaluate the immunogenicity and safety of live attenuated varicella vaccine (VR 795 Oka strain) in a two-dose, 3 months apart regimen.Methodology:Healthy children (⩾ 12 months and ⩽12 years; mean age: 4.4 years) of either sex were included. Geometric mean titers (GMT) were measured at baseline and 28 days post first- and second-dose, and seroprotection rates were measured 28 days post first and second dose. The incidence of breakthrough (BT) infections post vaccination was determined from 42 days post first and second dose of vaccine up to 12 months. Adverse events (AEs) were monitored and recorded throughout the study period.Results:Of 305 subjects enrolled, 217 were seronegative. The seroconversion rate (a change from a seronegative to a seropositive condition) was 93.3% post first-dose and 100% post two-doses. High levels (9 times) of GMT were reported since post first-dose to post second-dose in children aged 12–18 months, 18–60 months (99.43%); and in and above 60 months (99.02%). The extent of rise of anti-VZV IgG antibody titer post 28 days of first-dose at two-fold, three-fold and four-fold rise was 93.39%, 90.56% and 80.66%, respectively and 100% 4-fold rise post second-dose. A single case, a day after the first-dose of vaccination of mild BT infection, was observed after close contact with a severe case. AEs were mild and none of the serious AEs were related to the study drug.Conclusion:The two-dose schedule of varicella vaccine was safe and immunogenic when given 3 months apart. However, further comparative studies and follow up for both dosing schedules are needed to validate the advantage of early dosing.

Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-b]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-b]pyridin-2(3H)-one systems

A new series of phosphonylated triazolo[4,5-b]pyridine (1-deaza-8-azapurine), imidazo[4,5-b]pyridine (1-deazapurine) and imidazo[4,5-b]pyridin-2(3H)-one (1-deazapurin-8-one) were synthesized from 2-chloro-3-nitropyridine and selected diethyl ɷ-aminoalkylphosphonates followed by reduction of the nitro group and cyclization. In the final step O,O-diethylphosphonates were transformed into the corresponding phosphonic acids. All synthesized compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses and their cytotoxic potencies were also established. Compound 12f showed marginal activity against cytomegalovirus Davis strain (EC50 = 76.47 μM) in human embryonic lung (HEL) cells while compounds 10g (EC50 = 52.53 μM) and 12l (EC50 = 61.70 μM) were minimally active against the varicella-zoster virus Oka strain in HEL cells. Compounds under investigation were not cytotoxic at the maximum concentration evaluated (100 µM).

Transmission of Vaccine-Strain Varicella-Zoster Virus: A Systematic Review.

Live vaccines usually provide robust immunity but can transmit the vaccine virus. To assess the characteristics of secondary transmission of the vaccine-strain varicella-zoster virus (Oka strain; vOka) on the basis of the published experience with use of live varicella and zoster vaccines. Systematic review of Medline, Embase, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus databases for articles published through 2018. Articles that reported original data on vOka transmission from persons who received vaccines containing the live attenuated varicella-zoster virus. We abstracted data to describe vOka transmission by index patient's immune status, type (varicella or herpes zoster) and severity of illness, and whether transmission was laboratory confirmed. Twenty articles were included. We identified 13 patients with vOka varicella after transmission from 11 immunocompetent varicella vaccine recipients. In all instances, the vaccine recipient had a rash: 6 varicella-like and 5 herpes zoster. Transmission occurred mostly to household contacts. One additional case was not considered direct transmission from a vaccine recipient, but the mechanism was uncertain. Transmission from vaccinated immunocompromised children also occurred only if the vaccine recipient developed a rash postvaccination. Secondary cases of varicella caused by vOka were mild. It is likely that other vOka transmission cases remain unpublished. Healthy, vaccinated persons have minimal risk for transmitting vOka to contacts and only if a rash is present. Our findings support the existing recommendations for routine varicella vaccination and the guidance that persons with vaccine-related rash avoid contact with susceptible persons at high risk for severe varicella complications.

Comparison of the Whole-Genome Sequence of an Oka Varicella Vaccine from China with Other Oka Vaccine Strains Reveals Sites Putatively Critical for Vaccine Efficacy

Varicella-zoster virus (VZV) infection results in varicella mostly in children. Reactivation of the virus causes herpes zoster (HZ), mostly in adults. A live attenuated vaccine (vOka-Biken) was originally derived from the parental strain pOka. Several live attenuated vaccines based on the Oka strain are currently available worldwide. In China, varicella vaccines have been licensed by four manufacturers. In this study, we analyze the whole-genome sequence (WGS) of vOka-BK produced by Changchun BCHT Biotechnology also known as Baike. vOka-BK WGS was compared against the genomic sequences of four other Oka strains: pOka, vOka-Biken, vOka-Varilrix from GlaxoSmithKline, and vOka-Varivax from Merck & Co. A previous study identified 137 single nucleotide polymorphisms (SNPs) shared by all vOkas. The current analysis used these data as a reference to compare with vOka-BK WGS and focused on 54 SNPs located in the unique regions of the genome. Twenty-eight nonsynonymous substitutions were identified, ORF62 and ORF55 featuring the most amino acid changes with 9 and 3, respectively. Among the 54 SNPs, 10 had a different mutation profile in vOka-BK compared to the other three vaccines. A comparison with the clade 3 strain Ellen, known to be attenuated, identified three shared amino acid changes: *130R in ORF0 and R958G and S628G in ORF62. This analysis provides the first comparison of a Chinese varicella vaccine to the other vaccines available worldwide and identifies sites potentially critical for VZV vaccine efficacy.IMPORTANCE Varicella, also known as chickenpox, is a highly contagious disease, caused by varicella-zoster virus (VZV). Varicella is a common childhood disease that can be prevented by a live attenuated vaccine. The first available vaccine was derived from the parental Oka strain in Japan in 1974. Several live attenuated vaccines based on the Oka strain are currently available worldwide. Among the four vaccines produced in China, the vaccine manufactured by Changchun BCHT Biotechnology, also known as Baike, has been reported to be very efficacious. Comparative genomic analysis of the Baike vaccine with other Oka vaccine strains identified sites that might be involved in vaccine efficacy, as well as important for the biology of the virus.

Titration of cell-associated varicella-zoster virus with the MV9G reporter cell line for antiviral studies

Titration of the cell-associated virus (CAV) of varicella-zoster virus (VZV) is essential for antiviral studies. A VZV reporter cell line, MV9G, generated in our previous study expresses firefly luciferase upon CAV infection in a dose-dependent manner, suggesting that use of the cell line for titration is feasible. In this study, MeWo cells infected with VZV vaccine Oka (vOka) strain or with clinical isolates obtained from patients with varicella or zoster were used as CAV. A co-culture of MV9G cells with the virus-infected MeWo cells were set up and optimized for titration of CAV. Luciferase activities of MV9G cells measured as relative light units (RLUs) of chemiluminescence correlated well (r > 0.9, p < 0.05) both with quantities of viral DNAs measured by TaqMan PCR and with numbers of viral foci detected by immunostaining with a monoclonal antibody against VZV IE62. In addition, the usefulness of MV9G for antiviral studies was exemplified by treatment of the VZV-infected cells with various concentrations of acyclovir. Thus, the reporter cell-based titration of CAV by measuring the induced RLUs may be a reliable way to estimate viral foci and viral DNAs.

Xanthine-based acyclic nucleoside phosphonates with potent antiviral activity against varicella-zoster virus and human cytomegalovirus.

While noncanonic xanthine nucleotides XMP/dXMP play an important role in balancing and maintaining intracellular purine nucleotide pool as well as in potential mutagenesis, surprisingly, acyclic nucleoside phosphonates bearing a xanthine nucleobase have not been studied so far for their antiviral properties. Herein, we report the synthesis of a series of xanthine-based acyclic nucleoside phosphonates and evaluation of their activity against a wide range of DNA and RNA viruses. Two acyclic nucleoside phosphonates within the series, namely 9-[2-(phosphonomethoxy)ethyl]xanthine (PMEX) and 9-[3-hydroxy-2-(phosphonomethoxy)propyl]xanthine (HPMPX), were shown to possess activity against several human herpesviruses. The most potent compound was PMEX, a xanthine analogue of adefovir (PMEA). PMEX exhibited a single digit µM activity against VZV (EC50 = 2.6 µM, TK+ Oka strain) and HCMV (EC50 = 8.5 µM, Davis strain), while its hexadecyloxypropyl monoester derivative was active against HSV-1 and HSV-2 (EC50 values between 1.8 and 4.0 µM). In contrast to acyclovir, PMEX remained active against the TK– VZV 07–1 strain with EC50 = 4.58 µM. PMEX was suggested to act as an inhibitor of viral DNA polymerase and represents the first reported xanthine-based acyclic nucleoside phosphonate with potent antiviral properties.

Characterization of an anti-varicella-zoster virus compound that targets the portal protein encoded by ORF54.

An anti-varicella-zoster virus compound, a 5-chlorobenzo[b]thiophen derivative (45B5), was characterized. Its 50% effective concentration against the cell-free vaccine Oka strain and 50% cytotoxic concentration in human fibroblasts were 16.9 µM and more than 100 µM, respectively. Treatment with 45B5 decreased viral DNA synthesis and IE62 expression weakly but significantly. All 45B5-resistant viral clones isolated were found to have at least one mutation in ORF54 that encodes the portal protein. There were no effects on interaction between the portal and scaffold proteins. Thus, 45B5 may inhibit nuclear delivery of viral DNA.

Safety and immunogenicity of Bio Pox™, a live varicella vaccine (Oka strain) in Indian children: A comparative multicentric, randomized phase II/III clinical trial

ABSTRACTVaricella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasizing the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™[a] Please note that this article refers to the product named VARIVAX as manufactured by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB Life Sciences Limited, Mumbai, and not the product VARIVAX® owned by Merck Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have asked us to make clear that the product manufactured by Changchun Keygen Biological Products Ltd. is unrelated to and is not sponsored, endorsed or otherwise authorised by Merck Sharp & Dohme Corp., for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1–12 y (cohort I: 6–12 years, II:1–6 years) in 3 tertiary medical institutions. Antibodies were measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit. Seroconversion percentage in children having pre-vaccination anti VZV IgG titer <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio Pox™ and 77% for Varivax™ (p = 0.692). The seroconversion rate in the group receiving Bio Pox™ was non-inferior to the group that received Varivax™. There were mild local reactions for both the vaccines; none of the patient had fever or required hospitalization or medication. The Bio Pox™ was found to be safe and immunogenic in children against VZV infection.

The Glycoprotein B Cytoplasmic Domain Lysine Cluster Is Critical for Varicella-Zoster Virus Cell-Cell Fusion Regulation and Infection.

Varicella-zoster virus (VZV) is a ubiquitous pathogen that causes chickenpox and shingles. Individuals afflicted with shingles risk developing the painful condition of postherpetic neuralgia (PHN), which has been difficult to treat because the underlying cause is not well understood. Additional therapies are needed, as the current vaccine is not recommended for immunocompromised individuals and its efficacy decreases with the age of the recipient. VZV is known to induce the formation of multinuclear cells in neuronal tissue, which has been proposed to be a factor contributing to PHN. This study examines the role of a lysine cluster in the cytoplasmic domain of the VZV fusion protein, gB, in the formation of VZV induced multinuclear cells and in virus replication kinetics and spread. The findings further elucidate how VZV self-regulates multinuclear cell formation and may provide insight into the development of new PHN therapies.

Seroconversion and adverse reaction of live-attenuated (OKA strain) varicella vaccine

Background Live-attenuated varicella vaccine was used to pre-vent Shingle disease.Objective The aim of this study was to find out seroconversionrate and safety of this vaccine.Methods An open clinical trial was conducted on 313 children atCipto Mangunkusumo Hospital, Jakarta between March and Octo-ber 1998. The data were analyzed to distribution frequency andtables.Results Only 43 out of 356 (12.1%) children had positiveantivaricella antibody before vaccination. Seroconversion exami-nation by indirect immunoflouresence method was done only onrandomly 150 of 313 (50%) children due to financial limitation. Itwas found that 99.3% of patients had positive seroconversion.Among 298 children who were followed, the nature of symptom ofadverse reaction was mostly general than local. Only one patienthad local symptom after vaccination that appeared within 7 daysof the follow up period.Conclusion Varicella vaccine (OKA strain) gives highseroconversion rate with minimal adverse events

Seropositivity of Varicella zoster virus in vaccinated Korean children and MAV vaccine group

ABSTRACTIn 2005, a single-dose varicella vaccination was incorporated into the national immunization program in Korea. Although the Oka strain is the most commonly circulating Varicella zoster virus (VZV) genotype in Korea, a domestically manufactured vaccine based on the MAV strain is widely distributed in Korea. High vaccination coverage was achieved, but breakthrough infections were frequently reported. Therefore, in this study, we aimed to analyze the maintenance of immunity after single-dose vaccination and to compare the immunity provided by the MAV and Oka vaccines. Enzyme-linked immunosorbent assays of samples from 715 vaccinated Korean children were used to assess seropositivity rates against VZV. Additionally, fluorescent-antibody-to-membrane-antigen (FAMA) tests were performed in 35 individuals in the MAV vaccine group, and seropositivity rates against the Oka strain were determined. The progressive decrease of the seropositivity rate was demonstrated from ages 1 to 4 as follows: 65% in age 1, 59% in age 2, 53% in age 3, 49% in age 4. It then increased to 62% in age 5 and 70% in age 6. Both the MAV and Oka vaccine groups showed a progressive decrease of the seropositivity rate from the age of 1 to 4 years, but the MAV vaccine group had higher seropositivity rates. In FAMA test, the MAV group demonstrated 71% seropositivity against the Oka strain. This study indicates that immunity wanes after single-dose varicella vaccination and that the MAV vaccine is not inferior to the Oka vaccine in providing immunity against VZV. The MAV vaccine also induced cross-immunity against circulating Oka strain.

Dolor en el herpes zóster: prevención y tratamiento

Shingles is a painful rash that results from reactivation of latent varicella-zoster virus in the dorsal root ganglia or cranial nerves.In this article an update is presented on the prevention and pharmacological treatment of the secondary pain from the virus infection. The most effective way to prevent post-herpetic neuralgia and its consequences is the prevention of herpes itself. A live attenuated vaccine (the Oka strain varicella zoster virus) has been available for several years, and is approved in adults aged 50 years old. Although this vaccine has shown to be effective against herpes zoster and post-herpetic neuralgia, its effectiveness decreases with age and is contraindicated in patients with some form of immunosuppression. Today the recombinant vaccines provide an alternative, and may be administered to immunocompromised persons.

Synthesis, antiviral, cytotoxic and cytostatic evaluation of N 1-(phosphonoalkyl)uracil derivatives.

A series of N 1-(phosphonoalkyl)uracils was prepared in a two-step reaction sequence from ω-aminoalkylphosphonates and (E)-3-ethoxyacryloyl isocyanate followed by the uracil ring closure. Under standard conditions (NCS; NBS; I2/CAN) all N 1-(phosphonoalkyl)uracils were transformed into the respective 5-halogeno derivatives to be later benzoylated at N3. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses. One compound was slightly active against human cytomegalovirus in HEL cell cultures (EC50 = 45 μM) while another showed weak activity against varicella-zoster virus (TK+ VZV strain OKA and TK− VZV strain 07-1) with EC50 = 43 and 53 µM, respectively. In addition, several compounds exhibited noticeable inhibitory effects on the proliferation of human cervical carcinoma cells (HeLa) at a concentration lower than 200 μM.Graphical abstract