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Background: Ostreid herpesvirus-1 (OsHV-1) is the major bivalve pathogen associated with severe mortality events in a wide host range. In the early summer of 2012 and 2013, mass mortalities of blood clam (Scapharca broughtonii) broodstocks associated with a newly described variant of OsHV-1 (OsHV-1-SB) were reported. Methods: In this study, the complete genome sequence of the newly described variant was determined through the primer walking approach, and compared with those of the other two OsHV-1 variants. Results: OsHV-1-SB genome was found to contain 199, 354 bp nucleotides with 38.5 % G/C content, which is highly similar to those of acute viral necrosis virus (AVNV) and OsHV-1 reference type. A total of 123 open reading frames (ORFs) putatively encoding functional proteins were identified; eight of which were duplicated in the major repeat elements of the genome. The genomic organization of OsHV-1-SB could be represented as TRL-UL-IRL-IRS-US-TRS, which is different from that of OsHV-1 reference type and AVNV due to the deletion of a unique region (X, 1.5Kb) between IRL and IRS. The DNA sequence of OsHV-1-SB is 95.2 % and 97.3 % identical to that of OsHV-1 reference type and AVNV respectively. On the basis of nucleotide sequences of 32 ORFs in OsHV-1-SB and the other nine OsHV-1 variants, results from phylogenetic analysis also demonstrated that OsHV-1-SB is most closely related to AVNV. Conclusions: The determination of the genome of OsHV-1 with distinguished epidemiological features will aid in our better understanding of OsHV-1 diversity, and facilitate further research on the origin, evolution, and epidemiology of the virus. [ABSTRACT FROM AUTHOR]

Spring viremia of carp virus (SVCV) and koi herpesvirus (KHV) are highly contagious and pathogenic to cyprinid fish, causing enormous economic losses in aquaculture. Although DNA vaccines reported in recent years could induce protective immune responses in carps against these viruses via injection, there are a number of consequences and uncertainties related to DNA vaccination. Therefore, more effective and practical method to induce protective immunity such as oral administration would be highly desirable. In this study, we investigated the utilities of a genetically engineered Lactobacillus plantarum ( L . plantarum ) coexpressing glycoprotein (G) of SVCV and ORF81 protein of KHV as oral vaccine to induce protective immunity in carps via oral vaccination. The surface-displayed recombinant plasmid pYG-G-ORF81 was electroporated into L . plantarum , giving rise to LP/pYG-G-ORF81, where expression and localization of G-ORF81 fusion protein from the LP/pYG-G-ORF81 was identified by SDS-PAGE, Western blotting and immunofluorescence assay. Bait feed particles containing the LP/pYG-G-ORF81 were used as vaccine to immunize carps via gastrointestinal route. Compared to control groups, the carps orally immunized with the LP/pYG-G-ORF81 were induced significant levels of immunoglobulin M (IgM), and its immunogenicity was confirmed by viral loads reduction detected by PCR assay after virus challenge followed by an effective protection rate 71% in vaccinated carps and 53% in vaccinated koi until at days 65 post challenge, respectively. Our study here demonstrates, for the first time, the ability of recombinant L . plantarum as oral vaccine against SVCV and KHV infection in carps, suggesting a practical multivalent strategy for the control of spring viremia of carp and koi herpesvirus disease. [ABSTRACT FROM AUTHOR]

Background Febrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age. Methods All FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11–23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk. Results There were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5–12 days post receipt of MMR1 at 12 months (RI = 1.9 [95% CI: 1.3–2.9]), but not after VV at 18 months (RI = 0.6 [95% CI: 0.3–1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11–23 months (95% CI = 7–49 cases per 100,000) or 1 per 4167 doses. Conclusions Our study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013. [ABSTRACT FROM AUTHOR]

Gallid herpesvirus 2 (GaHV-2) is the alphaherpesvirus responsible for Marek's disease (MD), a T-cell lymphoma of chickens. The virulence of the GaHV-2 field strain is steadily increasing, but MD is still controlled by the CVI988/Rispens vaccine. We tried to determine distinguishing traits of the CVI988/Rispens vaccine by focusing on the 5′ end region of the latency-associated transcript (5′ LAT). It includes a variable number of 60-bp tandem repeats depending on the GaHV-2 strain. By analyzing six batches of vaccine, we showed that CVI988/Rispens consisted of a population of 5′ LAT molecular subtypes, all with deletions and lacking 60-bp tandem repeat motifs, with two major subtypes that probably constitute CVI988/Rispens markers. Serial passages in cell culture led to a substantial change in the frequency of CVI988/Rispens 5′ LAT subtypes, with non-deleted subtypes harboring up to four 60-bp repeats emerging during the last few passages. Dynamic changes in the distribution of 5′ LAT-deleted subtypes were also detected after infection of chickens. By contrast, the 5′ LAT region of the oncogenic clonal RB-1B strain, which was investigated at every step from the isolation of the clonal bacmid RB-1B DNA to the isolation of the ovarian lymphoma cell line, consisted of non-deleted 5′ LAT subtypes harboring at least two 60-bp repeats. Thus, vaccine and oncogenic GaHV-2 strains consist of specific populations of viral genomes that are constantly evolving in vivo and in vitro and providing potential markers for epidemiological surveys. [ABSTRACT FROM AUTHOR]

The article discusses the genetic manipulation of Marek's disease virus. It states that altering a gene in the virus leads to reduction in its virulence and when used in conjunction with Turkey Herpesvirus boosts protection against the virus. Topics include recombinant antibodies, in vitro studies, and genome sequencing of the virus.

A newly emerged tembusu virus that causes egg-drop has been affecting ducks in China since 2010. Currently, no vaccine is available for this disease. A live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine has been used routinely to control lethal DEV in ducks since the 1960s. Here, we constructed two recombinant DEVs by transfecting overlapping fosmid DNAs. One virus, rDEV-TE, expresses the truncated form of the envelope glycoprotein (TE) of duck tembusu virus (DTMUV), and the other virus, rDEV-PrM/TE, expresses both the TE and pre-membrane proteins (PrM). Animal study demonstrated that both recombinant viruses induced measurable anti-DTMUV neutralizing antibodies in ducks. After two doses of recombinant virus, rDEV-PrM/TE completely protected ducks from DTMUV challenge, whereas rDEV-TE only conferred partial protection. These results demonstrate that recombinant DEV expressing the TE and pre-membrane proteins is protective and can serve as a potential candidate vaccine to prevent DTMUV infection in ducks. [ABSTRACT FROM AUTHOR]

A significant portion of the world's population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) over a half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A∗24, HLA-B∗27, HLA-B∗53 and HLA-B∗58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B∗44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Recent evidence suggests that the epidemiology of herpes simplex viruses (HSVs) is changing because fewer HSV- 1 infections are acquired in childhood and increased sexual transmission of HSV-1 is reported. The objective of the study was to assess the seroprevalence of type-specific antibodies to HSV-1 and HSV-2 in the United States. Methods: We used the Western blot antibody screening data from a large phase HI vaccine efficacy trial (Herpevae Trial for Women) to assess the seroprevalence of type-specific antibodies to HSV-1 and HSV-2 in the United States. Results: The antibody status of 29,022 women (>31,000 women interviewed and then had their blood drawn for the HSV testing [29,022 women]) between the ages of 18 and 30 years in the United States revealed that increasing age was associated with increasing seroprevalence to HSV Overall, in asymptomatic women unaware of any HSV infection, HSV-1/-2 status was positive/negative in 45%, negative/positive in 5%, positive/positive in 7%, negative/negative in 38%, and indeterminate in 5%. HSV-1 infections were more common in Hispanic and non-Hispanic black women and in the US northeast and in individuals living in urban areas. HSV-2 was more common in non-Hispanic black women, the US south, and in urban areas. Conclusions: Seronegative status for both HSV-1 and HSV-2 was the second most common finding after positive antibody to HSV-1 but negative antibody to HSV-2. Despite recent changes in genital herpes epidemiology, most women acquired HSV-1 but not HSV-2 infections before 18 years of age. Among participants screened for study participation and who were unaware of any HSV-infection, progressively higher prevalence of the HSV-1 or HSV-2 antibody was observed in older subjects. Many women who test positive for HSV-1 and/or HSV-2 are unaware of their status. [ABSTRACT FROM AUTHOR]

Protection against infectious diseases can be obtained with vaccines generating immunogenic response through a combination of humoral and cellular immunity. In this study haematological and serum protein electrophoretic profiles of horses vaccinated against herpesvirus 1 (EHV-1) and 4 (EHV-4) were evaluated. Blood samples were collected from 16 horses before (T0), after 24h, 48h, 72h, 1st week, 2nd week and 3rd week (T1I, T2I, T3I, T7I, T14I and T21I) from the first EHV vaccine-dose administration as well as before (TPRE II ), and after 24h, 48h, 72h, 1st week, 2nd week, 3rd week and 4th week (T1II, T2II, T3II, T7II, T14II, T21II and T28II) from the EHV vaccine-booster. Total leukocyte values increased at T1I, T1II, T3II and T28II compared to T0 (P < .01). Higher lymphocytes and lower neutrophils values were found after first vaccine-dose and vaccine-booster administration compared to the T0 (P < .01). Monocytes showed higher values at T14II than T0 (P < .01). Higher serum values of total proteins, α1-, α-2-, β1-, β2- and γ-globulins were found in horses after first vaccine-dose and vaccine-booster administration (P < .01). Gathered results suggest that horses vaccinated against EHV1 and EHV-4 exhibited a dynamic change of WBC, lymphocytes, neutrophils and monocytes. Moreover, the analysis of serum electrophoresis pattern suggested that EHV vaccination induced the development of inflammation and antibody response in vaccinated horses as highlighted by the increase of α-, β- and γ-globulin fractions. These changes probably reflect the systemic immunological adaptation of animals to EHV vaccine., (Copyright © 2022. Published by Elsevier Inc.)

Varicella zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (HZ [shingles]). Clinical observations suggest that VZV-specific T cell immunity plays a more critical role than humoral immunity in the prevention of VZV reactivation and development of herpes zoster. Although numerous studies have characterized T cell responses directed against select VZV open reading frames (ORFs), a comprehensive analysis of the T cell response to the entire VZV genome has not yet been conducted. We have recently shown that intrabronchial inoculation of young rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we characterized the specificity of T cell responses during acute and latent SVV infection. Animals generated a robust and broad T cell response directed against both structural and nonstructural viral proteins during acute infection in bronchoalveolar lavage (BAL) fluid and peripheral blood. During latency, T cell responses were detected only in the BAL fluid and were lower and more restricted than those observed during acute infection. Interestingly, we identified a small set of ORFs that were immunogenic during both acute and latent infection in the BAL fluid. Given the close genome relatedness of SVV and VZV, our studies highlight immunogenic ORFs that may be further investigated as potential components of novel VZV vaccines that specifically boost T cell immunity. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection is now the commonest congenital form of infective neurological handicap, recognized by the Institute of Medicine as the leading priority for the developed world in congenital infection. In the absence of an effective vaccine, universal screening for CMV in pregnancy has been proposed, in order that primary infection could be diagnosed and- potentially- the burden of disability due to congenital CMV prevented. Discussion: Universal screening for CMV to identify seronegative women at the beginning of pregnancy could potentially reduce the burden of congenital CMV in one of three ways. The risk of acquiring the infection during pregnancy has been shown to be reduced by institution of simple hygiene measures (primary prevention). Among women who seroconvert during pregnancy, CMV hyperimmune globulin (CMV HIG) shows promise in reducing the risk of perinatal transmission (secondary prevention), and CMV HIG and/ or antivirals may be effective in reducing the risk of clinical sequelae among those known to be infected (tertiary prevention). The reports from these studies have re-ignited interest in universal screening for CMV, but against the potential benefit of these exciting therapies needs to be weighed the challenges associated with the implementation of any universal screening in pregnancy. These include; the optimal test, and timing of screening, to maximize detection; an approach to the management of equivocal results, and the cost effectiveness of the proposed screening program. In this article, we provide an overview of current knowledge and ongoing trials in the prevention, diagnosis and management of congenital CMV. Recognising that CMV screening is already being offered to many patients on an ad hoc basis, we also provide a management algorithm to guide clinicians and assist in counseling patients. Summary: We suggest that- on the basis of current data- the criteria necessary to recommend universal screening for CMV are not yet met, but this position is likely to change if trials currently underway confirm that CMV HIG and/ or antivirals are effective in reducing the burden of congenital CMV disease. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ) is the painful reactivation of latent varicella zoster virus infection. The incidence of HZ may be increased in some autoimmune diseases, including systemic lupus erythematosus (SLE). We examined the incidence and risk factors for HZ in a prospective cohort of patients with physician-diagnosed SLE compared to those diagnosed with non-inflammatory musculoskeletal conditions (MSK). After excluding participants with a history of prior HZ at enrollment, we followed 1485 SLE patients and 2775 MSK with semi-annual mailed questionnaires for incident HZ between 2001 and 2010. Age-adjusted incidences were calculated for each group and Cox proportional hazard models were used to identify predictors of HZ. Zostavax® vaccination rates were compared between groups.Participants had a mean age of 60 years at enrollment, with 13.9 years of disease. SLE patients had more HZ at all ages, with an age-adjusted incidence of 12.0/1000 person-years compared to MSK (8.7/1000 person-years) and a hazard ratio of 1.7 (95% CI 1.08–2.71) for SLE. Increasing age and reduced functional status were independent predictors of HZ. In SLE, prednisone and mycophenolate mofetil use conferred additional risk. SLE had the lowest HZ vaccination rates among age-eligible subjects. [ABSTRACT FROM PUBLISHER]

Abstract: Emerging evidence suggests that cats infected with feline herpesvirus-1 (FHV-1) may experience a brief viremic phase. The objective of this study was to determine whether natural routes of FHV-1 inoculation could result in viremic transmission of infectious virus to connective tissues (cortical bone, tendon). Three specific pathogen-free cats were experimentally inoculated with FHV-1 via a combined mucosal (oronasal, ocular) route. Cats were euthanized at the peak of clinical signs to aseptically harvest tissues (cortical bone, tendon, trachea/tongue) for co-culture with a susceptible cell line to promote spread of infectious virus. Viral infection of Crandall-Rees feline kidney cells was microscopically visualized by cytopathic effect (CPE). Additionally, co-culture DNA was extracted either at the point of CPE or 16 days of culture without evidence of CPE, to amplify FHV-1 glycoprotein B gene using real-time PCR. Infectious virus was detected in distant cortical bone (two cats, moderate to severe clinical signs) and tendon (one cat, severe clinical signs). Direct infection of mucosal (trachea, tongue) tissues also was confirmed in these two cats. In contrast, all co-cultured tissues from the third cat (mild clinical signs) were negative for FHV-1 by CPE and PCR. Results of this study demonstrated that early primary FHV-1 viremia may be distributed to distant connective tissues. [Copyright &y& Elsevier]

Abstract: In recent years, there been significant progress toward develop more efficient vaccines. Different compounds with adjuvant capacity have been tested; however, no compound has emerged that suitable for universal use. Several efforts have been made to produce effective vaccines against Bovine herpesvirus 5 (BoHV-5), an important cattle pathogen. In this study we examine the use the probiotic Bacillus cereus var. Toyoi as a potential adjuvant to improve BoHV-5 vaccine efficacy. We observed in the supplemented animals a systemic enhanced IgG antibody response toward Th1, and increased IFN-γ, IL-12 and IL-10 cytokines mRNA levels. These results suggest that this probiotic could provide a promising means of improving vaccine efficacy, particularly those vaccines that rely on a cell-mediated immune response. [Copyright &y& Elsevier]

Abstract: A recombinant bovine herpesvirus 5 lacking thymidine kinase and glycoprotein E genes (BoHV-5gEΔTKΔ) was evaluated as a live experimental vaccine. In a first experiment, ten-months-old calves were vaccinated intramuscularly (n =9) or remained as controls (n =8) and 42 days later were challenged with BoHV-5 or BoHV-1 intranasally. The four control calves challenged with BoHV-5 developed severe depression and neurological signs and were euthanized in extremis at days 13 and 14 pos-infection (pi); the five vaccinated animals challenged with BoHV-5 remained healthy. The titers of virus shedding were reduced (p <0.01) from days 3 to 7 post-infection (pi) in vaccinated animals. Control and vaccinated calves challenged with BoHV-1 presented mild transient respiratory signs; yet the magnitude of virus shedding was reduced (p <0.05) in vaccinated animals (days 5, 9 and 11pi). In a second experiment, young calves (100–120 days-old) were vaccinated (n =15) or kept as controls (n =5) and subsequently challenged with a BoHV-1 isolate. Control calves developed moderate to severe rhinitis and respiratory distress; two were euthanized in extremis at days 5 and 9 pi, respectively. In contrast, vaccinated animals were protected from challenge and only a few developed mild and transient nasal signs. The duration and titers of virus shedding after challenge were reduced (p <0.05) in vaccinated animals comparing to controls. In both experiments, vaccinated animals developed antibodies to gE only after challenge. These results demonstrate homologous and heterologous protection and are promising towards the use of the recombinant BoHV-5gEΔTKΔ in vaccine formulations to control BoHV-5 and BoHV-1 infections. [Copyright &y& Elsevier]

Abstract: Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes acute respiratory disease in poultry. Live attenuated ILTV vaccines have been used extensively to help control outbreaks of disease. Two Australian-origin attenuated vaccine strains, SA2 and A20 ILTV, are commercially available and are in frequent use in Australia. Both these vaccines are of chicken embryo origin (CEO). The A20 ILTV strain was developed from the SA2 ILTV strain by sequential passage of SA2 ILTV in tissue culture in order to reduce its residual virulence. Previous studies in our laboratories have demonstrated the greater attenuation of A20 ILTV under controlled experimental conditions, but the genetic basis of the in vivo phenotypes of A20 and SA2 ILTV has not been elucidated. In this study, the genetic differences between A20 and SA2 ILTV were examined by performing complete genome sequencing and comparative analysis. The genome sequences were also compared to a reference sequence from another CEO ILTV vaccine (Serva ILTV: GenBank accession number HQ_630064) of European-origin. Additional in ovo studies to assess cell to cell spread were performed in order to allow further comparisons of the pathogenicity of SA2 and A20 ILTV. The sequencing results showed that the genome sizes of SA2 and A20 ILTV were 152,975 and 152,978bp, respectively, while Serva ILTV had a genome size of 152,630bp. The genomes of SA2 and A20 ILTV shared 99.9% nucleotide sequence identity with each other, but only 99.2% identity with Serva ILTV. In complete genome alignments between SA2 and A20 ILTV, a total of 24 single nucleotide polymorphisms (SNPs) were identified, but only two of these were non-synonymous. These were located in the ORF B and UL15 genes. Four indels were detected in non-coding regions. The findings from this study demonstrate the general genetic stability of ILTV, but also show that non-synonymous changes in the ORF B and UL15 genes have arisen following tissue culture passage of SA2 ILTV to produce the A20 vaccine. It is likely that these non-synonymous changes are related to the greater attenuation of A20 ILTV compared to SA2 ILTV, and to the reduced ability of A20 ILTV to spread from cell to cell, as observed in this study. The results from this study also demonstrate the divergence between the genomes of the Australian-origin ILTV vaccine strains and the Serva vaccine strain. [Copyright &y& Elsevier]

Objective--To assess the serologic response of calves to inactivated and modified-live (ML) Mannheimia haemolytica (MH) preparations given alone and concurrently with combination viral vaccines containing ML bovine herpesvirus type 1 (BHV-1). Animals--642 calves seronegative for BHV-I. Procedures--In experiment 1, 192 calves received 1 of 3 MH preparations alone or concurrently received 1 of 3 MH preparations and 1 of 4 combination viral vaccines. In experiment 2, 450 calves received 1 of 4 MH preparations alone or concurrently received 1 of 4 MH preparations and 1 of 5 combination viral vaccines. Pretreatment and posttreatment blood samples were processed to obtain serum, which was analyzed to detect concentrations of antibodies against MH leukotoxin and BHV-1. Results--In experiment 1, antibody titers against MH leukotoxin in calves receiving MH and ML virus vaccine appeared decreased, albeit nonsignificantly, compared with titers for calves receiving MH preparations alone. In experiment 2, all groups (except for 1) concurrently receiving an MH preparation and viral vaccine had a significant decrease in antibodies against MH leukotoxin. In both experiments, there was a significant decrease in the number of calves responding to MH leukotoxin when ML viral vaccine was coadministered. Conclusions and Clinical Relevance--Coadministration of ML BHV-1 and MH preparations interfered with the serologic response to MH leukotoxin in calves seronegative for BHV-1. Serologic response to MH leukotoxin may be substantially improved in seronegative calves when MH vaccination is delayed until after calves have received a dose of ML BHV-1 vaccine. [ABSTRACT FROM AUTHOR]

Abstract: A major challenge for poultry vaccination is the design of vaccines that protect against multiple pathogens via a single protective dose delivered through mass vaccination methods. In this investigation, we examined herpesvirus of turkeys (HVT) as a vaccine vector for delivery of haemagglutinin (HA) antigen of highly pathogenic H7N1 avian influenza virus that can act as a dual vaccine against avian influenza and Marek''s disease. The HVT vector was developed using reverse genetics based on an infectious bacterial artificial chromosome (BAC) clone of HVT. The BAC carrying the HVT genome was genetically modified to express the HA gene of a highly pathogenic H7N1 virus. The resultant recombinant BAC construct containing the modified HVT sequence was transfected into chicken embryo fibroblast (CEF) cells, and HVT recombinants (rHVT-H7HA) harbouring the H7N1 HA were recovered. Analysis of cultured CEF cells infected with the rHVT-H7HA showed that HA was expressed and that the rescued rHVT-H7HA stocks were stable during several in vitro passages with no difference in growth kinetics compared with the parent HVT. Immunisation of one-day-old chicks with rHVT-H7HA induced H7-specific antibodies and protected chickens challenged with homologous H7N1 virus against virus shedding, clinical disease and death. This vaccine supports differentiation between infected and vaccinated animals (DIVA) vaccination strategies because no nucleoprotein-(NP) specific antibodies were detected in the rHVT-H7HA vaccinated birds. The rHVT-H7HA not only provided protection against a lethal challenge with highly pathogenic H7N1 virus but also against highly virulent Marek''s disease virus and can be used as a DIVA vaccine. [Copyright &y& Elsevier]

Abstract: In this study, we have compared the protection afforded by a recombinant turkey herpesvirus vaccine expressing the H5 gene from a clade 2.2 H5N1 strain (rHVT-H5) and a Mexican-origin H5N2 inactivated vaccine, alone or in combination, against two antigenically divergent H5N1 Egyptian strains isolated in 2007 and 2008. Our results confirm the existence of a major antigenic drift among the Egyptian H5N1 strains such that, although protection against the “classical” 2007 HPAI H5N1 Egyptian strain could be obtained with both types of vaccines, only vaccination with the rHVT-H5 vaccine protected against challenge with the “variant” 2008 HPAI H5N1 Egyptian strain. [Copyright &y& Elsevier]

Abstract: Bovine herpesvirus type 5 (BoHV-5) is the causative agent of bovine herpetic encephalitis. In countries where BoHV-5 is prevalent, attempts to vaccinate cattle to prevent clinical signs from BoHV-5-induced disease have relied essentially on vaccination with BoHV-1 vaccines. However, such practice has been shown not to confer full protection to BoHV-5 challenge. In the present study, an inactivated, oil adjuvanted vaccine prepared with a recombinant BoHV-5 from which the genes coding for glycoprotein I (gI), glycoprotein E (gE) and membrane protein US9 were deleted (BoHV-5 gI/gE/US9−), was evaluated in cattle in a vaccination/challenge experiment. The vaccine was prepared from a virus suspension containing a pre-inactivation antigenic mass equivalent to 107.69 TCID50/dose. Three mL of the inactivated vaccine were administered subcutaneously to eight calves serologically negative for BoHV-5 (vaccinated group). Four other calves were mock-vaccinated with an equivalent preparation without viral antigens (control group). Both groups were boostered 28 days later. Neither clinical signs of disease nor adverse effects were observed during or after vaccination. A specific serological response, revealed by the development of neutralizing antibodies, was detected in all vaccinated animals after the first dose of vaccine, whereas control animals remained seronegative. Calves were subsequently challenged on day 77 post-vaccination (pv) with 109.25 TCID50 of the wild-type BoHV-5 (parental strain EVI 88/95). After challenge, vaccinated cattle displayed mild signs of respiratory disease, whereas the control group developed respiratory disease and severe encephalitis, which led to culling of 2/4 calves. Searches for viral DNA in the central nervous system (CNS) of vaccinated calves indicated that wild-type BoHV-5 did not replicate, whereas in CNS tissues of calves on the control group, viral DNA was widely distributed. BoHV-5 shedding in nasal secretions was significantly lower in vaccinated calves than in the control group on days 2, 3, 4 and 6 post-challenge (pc). In addition, the duration of virus shedding was significantly shorter in the vaccinated (7 days) than in controls (12 days). Attempts to reactivate latent infection by administration of dexamethasone at 147 days pv led to recrudescence of mild signs of respiratory disease in both vaccinated and control groups. Infectious virus shedding in nasal secretions was detected at reactivation and was significantly lower in vaccinated cattle than in controls on days 11–13 post-reactivation (pr). It is concluded that the inactivated vaccine prepared with the BoHV-5 gI/gE/US9− recombinant was capable of conferring protection to encephalitis when vaccinated cattle were challenged with a large infectious dose of the parental wild type BoHV-5. However, it did not avoid the establishment of latency nor impeded dexamethasone-induced reactivation of the virus, despite a significant reduction in virus shedding after challenge and at reactivation on vaccinated calves. [Copyright &y& Elsevier]

An experimental inactivated vaccine against bovine herpesvirus-1 (BoHV-1) was produced aiming to evaluate the systemic and local antibody responses in 12 seronegative heifers, after vaccination and revaccination. Serum samples were submitted to virus neutralization assay and to ELISA test for detection of IgG1 and IgG2 isotypes. Nasal secretion samples were submitted to the same ELISA test for detection of IgG1 and IgG2 isotypes. The results showed that moderate to high neutralizing titres and IgG1 and IgG2 antibody responses were induced after the second vaccination in the serum and in nasal secretions up to 114 days post vaccination. IgG2 antibodies were the prevalent isotype for most of the post-vaccination period. The results indicate that BoHV-1 experimental inactivated vaccine elicited potentially protective IgG1 and IgG2 antibody levels, both in the systemic and mucosal compartments. [ABSTRACT FROM AUTHOR]

The article focuses on a retrospective cohort study which evaluated the risk of herpes zoster after receipt of herpes zoster vaccine among individuals in general practice settings. Immunocompetent community-dwelling adults aged 60 years or older were used in the study. It was found that the risk of herpes zoster vary by vaccination status to a greater magnitude than the risk of unrelated acute medical conditions. The study also observed a reduced risk among all age strata and among individuals with chronic diseases.

Background: Herpes simplex type II (HSV-2) is a member of the family herpesviridae. Human infection with this double stranded linear DNA virus causes genital ulcerative disease and existing treatment options only serve to resolve the symptomatology (ulcers) associated with active HSV-2 infection but do not eliminate latent virus. As a result, infection with HSV-2 follows a life-long relapsing (active versus latent) course. On the basis of a primitive bacterium anti-phage DNA defense, the restriction modification (R-M) system, we previously identified the Escherichia coli restriction enzyme (REase) EcoRII as a novel peptide to excise or irreversibly disrupt latent HSV-2 DNA from infected cells. However, sequences of the site specificity palindrome of EcoRII 5'-CCWGG-3' (W = A or T) are equally present within the human genome and are a potential source of host-genome toxicity. This feature has limited previous HSV- 2 EcoRII based therapeutic models to microbicides only, and highlights the need to engineer artificial REases (zinc finger nucleases-ZFNs) with specificity to HSV-2 genomic-DNA only. Herein, the therapeutic-potential of zinc finger arrays (ZFAs) and ZFNs is identified and modeled, with unique specificity to the HSV-2 genome. Methods and results: Using the whole genome of HSV-2 strain HG52 (Dolan A et al.,), and with the ZFN-consortium's CoDA-ZiFiT software pre-set at default, more than 28,000 ZFAs with specificity to HSV-2 DNA were identified. Using computational assembly (through in-silico linkage to the Flavobacterium okeanokoites endonuclease Fok I of the type IIS class), 684 ZFNs with specificity to the HSV-2 genome, were constructed. Graphic-analysis of the HSV-2 genome-cleavage pattern using the aforeidentified ZFNs revealed that the highest cleavage-incidence occurred within the 30,950 base-pairs (~between the genomic context coordinates 0.80 and 1.00) at the 3' end of the HSV-2 genome. At approximately 3,095 bp before and after the 5' and 3' ends of the HSV-2 genome (genomic context coordinates 0.02 and 0.98, respectively) were specificity sites of ZFNs suited for the complete excision of over 60% of HSV-2 genomic material from within infected human cells, through the process of non-homologous end joining (NHEJ). Furthermore, a model concerning a recombinant (ICP10-PK mutant) replication competent HSV-2 viral vector for delivering and transducing a diploid copy (or pair) of the HSV-2-genome-specific ZFN genotype within neuronal tissue, is presented. Conclusion: ZFNs with specificity to HSV-2 genomic DNA that are precursors of novel host-genome expressed HSV-2 gene-therapeutics or vaccines were identified. [ABSTRACT FROM AUTHOR]

Herpes simplex virus 1 (HSV-1) ICP0- mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV- 1 (Virol J, 2006, 3:44). If an ICP0- mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate against genital herpes. The current study was initiated to explore this possibility. Several HSV-2 ICP0- mutant viruses were constructed and evaluated in terms of three parameters: i. interferon-sensitivity; ii. virulence in mice; and iii. capacity to elicit protective immunity against HSV-2. One ICP0- mutant virus in particular, HSV-2 0ΔNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0ΔNLS was interferon-sensitive in cultured cells. HSV-2 0ΔNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent host immune response. HSV-2 0ΔNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0ΔNLS consistently mounted an HSV-specific IgG antibody response, and were consistently protected against lethal challenge with wild-type HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0- mutant viruses merit consideration for their potential to prevent the spread of HSV-2 and genital herpes. [ABSTRACT FROM AUTHOR]

Purpose. Herpes zoster, herpes zoster vaccine, and the cost-effectiveness of the vaccine are reviewed. Summary. Herpes zoster infection is estimated to affect one in three people during their lifetime. Two thirds of people who develop this disease are over age 60 years. Postherpetic neuralgia (PHN) is the most common complication of herpes zoster, occurring in 10-18% of patients. The associated chronic pain can be very debilitating, affecting patients' quality of life. The pain may last for months or years and is difficult to treat, leading to increased health care costs and morbidity. To prevent herpes zoster, a live attenuated vaccine was developed and approved for marketing in 2006 for individuals age ?60 years. The safety and efficacy of the vaccine were evaluated in the Shingles Prevention Study in 38,546 adults age ?60 years. Compared with placebo, administration of the vaccine resulted in a 51.3% reduction in the incidence of herpes zoster and a 66.5% reduction in the incidence of PHN (p < 0.001 for both comparisons). A single dose of the vaccine is approximately $162 and is not covered by all insurance plans. Several studies evaluated the cost-effectiveness of the vaccine, which was found to be most beneficial in individuals age 70 years or older. The use of the vaccine appears to reduce health care costs and protect the public health. Conclusion. The herpes zoster vaccine is effective in preventing herpes zoster and decreasing the incidence of complications. However, insurance coverage may hinder eligible patients from receiving the vaccination. [ABSTRACT FROM AUTHOR]

Abstract: A vaccine for Kaposi''s sarcoma-associated herpesvirus (KSHV) is not currently available. To obtain the fundamental data in animals for vaccine development, KSHV particles were immunized to Balb/c mice through intraperitoneal and intranasal routes in the present study. Intranasal immunization with KSHV induced IgA to KSHV in not only serum, but also nasal wash fluid and saliva. A neutralization assay using recombinant KSHV that expressed green fluorescent protein revealed that nasal wash fluid and saliva from the KSHV-immunized mice neutralized KSHV infection to human embryonic kidney 293 cells in vitro in a dose-dependent manner to KSHV copies immunized. The serum and nasal wash fluid of KSHV-encoded K8.1 protein-immunized mice neutralized KSHV infection to 293 cells in vitro. These data suggest a possibility of mucosal vaccine for prophylaxis of KSHV infection. [Copyright &y& Elsevier]

Abstract: Vaccination is commonly used to control equine respiratory pathogens such as equine herpesvirus type 1 (EHV-1) and equine influenza virus (EIV). Here, we describe the generation and characterization of a recombinant EHV-1 modified live virus vaccine (MLV) based on a recent abortogenic EHV-1 strain, NY03. The immunogenicity and efficacy of the MLV was tested in horses in an EHV-1 vaccination/challenge experiment using the highly virulent neurovirulent EHV-1 strain OH03. Induction of a robust EHV-1-specific immune response was observed. Upon challenge infection, vaccinated horses were partially protected against disease as demonstrated by a significant reduction in clinical signs, nasal shedding and viremia levels. In addition, the NY03-based MLV was used to express the EIV H3 protein and immunogenicity was tested in horses. Expression of H3 was readily detected in NY03-H3-infected cells in vitro. Vaccination of horses resulted in the induction of a robust serological immune responses against two recent but genetically distinct EIV representatives, VA05 and NY-99, which were above the threshold predicted to be protective against development of clinical disease. [Copyright &y& Elsevier]

Abstract: Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) binds complement component C3b and inhibits complement-mediated immunity. HSV-1 glycoprotein D (gD-1) is a potent immunogen and a candidate antigen for a subunit vaccine. We evaluated whether combined immunization with gD-1 and gC-1 provides better protection against challenge than gD-1 alone based on antibodies to gC-1 preventing HSV-1-mediated immune evasion. IgG purified from mice immunized with gC-1 blocked C3b binding to gC-1 and greatly increased neutralization by gD-1 IgG in the presence of complement. Passive transfer of gC-1 IgG protected complement intact mice against HSV-1 challenge but not C3 knockout mice, indicating that gC-1 antibody activity in vivo is complement-dependent. Immunizing mice with gD-1 and gC-1 provided better protection than gD-1 alone in preventing zosteriform disease and infection of dorsal root ganglia. Therefore, gC-1 immunization prevents HSV-1 evasion from complement and enhances the protection provided by gD-1 immunization. [Copyright &y& Elsevier]

Abstract: Live attenuated herpesvirus vaccines such as herpesvirus of turkey (HVT) have been used since 1970 for the control of Marek''s disease (MD), a highly infectious lymphoproliferative disease of poultry. Despite the success of these vaccines in reducing losses from the disease, Marek''s disease virus (MDV) strains have shown a continuing increase in virulence, presumably due to the inability of the current vaccines in preventing MDV replication. The highly specific and effective nature of RNA interference (RNAi) makes this technology particularly attractive for new antiviral strategies. In order to exploit the power of RNAi-mediated suppression of MDV replication in vivo delivered through existing vaccines, we engineered recombinant HVT expressing short hairpin RNA (shRNA) against MDV genes gB and UL29. The levels of protection induced by the RNAi-expressing HVT against virulent virus challenge were similar to the parent pHVT3 virus. However, chickens vaccinated with recombinant HVT expressing shRNA showed moderate reduction of challenge virus replication in blood and feather samples. Delivery of RNAi-based gene silencing through live attenuated vaccines for reducing replication of pathogenic viruses is a novel approach for the control of infectious diseases. [Copyright &y& Elsevier]

Abstract: As part of a series of studies on vaccine acceptance, we assessed determinants of compliance of the community-dwelling elderly with herpes zoster (HZ) vaccination in an existing influenza vaccination program. General practitioners (GPs) sent out a questionnaire to 1778 patients aged ≥65 years, and offered them free HZ vaccination simultaneously with the yearly influenza vaccination. In all, 690 patients (39%) were vaccinated against HZ; 1349 patients (76%) accepted influenza vaccination. Determinants of non-compliance with HZ vaccination were perceived lack of recommendation by the GP, unwillingness to comply with the doctor''s advice, perception of low risk of contracting HZ, perception of short pain duration of HZ, and the opinion that vaccinations weaken one''s natural defenses. The same determinants were associated with non-compliance with both vaccinations, but objections in general towards vaccination, a high education and difficulties to visit GPs were also important. Uptake of HZ vaccination was rather low and more data on (cost-)effectiveness might encourage GPs to offer HZ vaccination to their patients. [Copyright &y& Elsevier]

Abstract: The recent advances in molecular genetics, pathogenesis and immunology have provided an optimal framework for developing novel approaches in the rational design of vaccines effective against viral epizootic diseases. This paper reviews most of the viral-vector based antigen delivery systems (ADSs) recently developed for vaccine testing in veterinary species, including attenuated virus and DNA and RNA viral vectors. Besides their usefulness in vaccinology, these ADSs constitute invaluable tools to researchers for understanding the nature of protective responses in different species, opening the possibility of modulating or potentiating relevant immune mechanisms involved in protection. [Copyright &y& Elsevier]

Abstract: A bovine herpesvirus 4 was isolated from the milk cell fraction of a healthy cow and his full genome cloned as a bacterial artificial chromosome. So cloned viral genome was used as a vector platform to deliver in vitro and in vivo an optimized secreted chimeric peptide obtained by the fusion of the bovine viral diarrhoea virus glycoprotein E2 ectodomain with the bovine herpesvirus 1 glycoprotein D ectodomain. Recombinant virus infected cells robustly expressed and secreted the chimeric peptide into the culture medium and inoculated animals with the recombinant virus successfully responded toward antigens, gE2 and gD. Thus, this work has implications for the development of safe and effective polyvalent vaccines. [Copyright &y& Elsevier]

Background: Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level. Methods and Findings: A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub- Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence. Conclusions: HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships. [ABSTRACT FROM AUTHOR]

Objectives To examine the effects of varying the doses of turkey herpesvirus (HVT) vaccine and Marek's disease virus (MDV) challenge at two intervals after vaccination on the protection of chickens against challenge with MDV. Design and procedure Experiment 1, a dose response study, consisted of 11 doses of HVT vaccine administered at hatch followed by challenge with 100 plaque forming units (pfu) of MDV 5 days post vaccination. Experiment 2, a 2 × 6 × 2 factorial design, included two HVT vaccine types, six different doses of HVT vaccine and 50 pfu and 200 pfu of MDV challenge 2 days post vaccination. All chickens were reared up to day 56 post challenge when all survivors were killed humanely. Dead and killed chickens were examined for gross MD tumours. Results Experiment 1 showed a significant positive linear relationship between dose of HVT vaccine and protective index in chickens challenged 5 days post vaccination. However the range of protective index observed was limited. In Experiment 2 neither HVT vaccine provided significant protection at any dose. There was no significant effect of vaccine type or MDV challenge dose on overall protection against challenge. Chickens challenged with 200 pfu of MDV had significantly higher mortality and MD incidence than those with 50 pfu. Conclusions HVT vaccine dose had a significant impact on protective index, but vaccination to challenge interval appeared to have greater impact on the protective efficacy of vaccination. A fourfold increase in challenge dose increased mortality rate and incidence of MD. [ABSTRACT FROM AUTHOR]

The performance of a live marker vaccine for bovine herpesvirus type I (BHv-1) was studied in the field in three European Union countries with different farming conditions. The progress in the eradication of the virus was followed in a large herd in Germany and one in Italy, and a major serological survey involving 147 farms was conducted in Hungary. Commercial batches of the same vaccine were used in all three studies. The herds were vaccinated according to agreed protocols and the animals' BHV-1 antibody status was determined at local institutes by using commercial glycoprotein B (gB)- and glycoprotein E (gE)-ELISAs. In all three studies, the seroprevalence of BHV-1 gE decreased progressively. Given the starting conditions and the long duration of the studies, reactivation events and virus circulation would have been more likely to have occurred if the herds had not been vaccinated. [ABSTRACT FROM AUTHOR]

The article discusses whether an older man should receive the varicella-zoster vaccine to prevent herpes zoster, or shingles. The varicella-zoster virus is a herpesvirus that can cause chickenpox or shingles. The pathophysiology of the varicella-zoster virus and the effect of the vaccine are reviewed. Clinical studies that show that the varicella-zoster vaccine improves immunity in older people are reviewed. Adverse effects of the vaccine include rashes at the injection site, erythema, and pain or tenderness. The authors of the report feel that the immunocompetent person described should receive the vaccine as a preventive measure.

Abstract: Despite recent technological advances in vaccine production, most vaccines depend on the association with adjuvant substances. In this study, propolis, which has been attracting the attention of researchers due to its bioactive properties, was evaluated as an immunological adjuvant. The association of 40mg/dose of an ethanolic extract of green propolis with an inactivated oil vaccine against bovine herpesvirus type 5 (BoHV-5), resulted in a significant increase (P <0.01) in the neutralizing antibody levels, comparing to the bovines that received the same vaccine without propolis. Besides, propolis increased the percentage of animals with high antibody titers (above 32). Phenolic compounds such as artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) and the derivatives of cinnamic acid besides other flavonoid substances were abundant in the propolis extract used, and they could be the main substances with adjuvant action. The effect of the green propolis extract on the humoral immune response can be exploited in the development of new vaccines. [Copyright &y& Elsevier]