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We constructed turkey herpesvirus (HVT) vector vaccines in which the VP2 gene of infectious bursal disease virus (IBDV) was inserted into the HVT genome in the following regions: UL3-4, UL22-23, UL45-46, and US10-SORF3. We then evaluated the relationship between the gene insertion site and the capacity of the virus to elicit antibodies. rHVT/IBD (US10) showed good growth activity in vitro, with growth comparable to that of the parent HVT. On the other hand, rHVT/IBD (UL3-4), rHVT/IBD (UL22-23), and rHVT/IBD (UL45-46) exhibited decreased growth activity in chicken embryo fibroblast (CEF) cells compared to the parent HVT. However, the rHVT/IBD (US10) elicited lower levels of virus-neutralizing (VN) antibodies compared to the other constructs. rHVT/IBD (UL3-4) and rHVT/IBD (UL45-46) appeared to be similar in their ability to elicit VN antibodies. Based on the results of in vitro and in vivo assays, rHVT/IBD (UL3-4) was selected for further testing. In a challenge assay, rHVT/IBD (UL3-4) protected chickens from challenge with virulent Marek's disease virus serotype 1 and IBDV. In conclusion, the site of gene insertion may have a strong effect on the growth of the vector virus in vitro and its antibody-eliciting capacity. Insertions in the UL3-4 region permitted a balance between growth activity and VN-antibody-eliciting capacity, and this region might therefore be an appropriate insertion site for IBDV VP2. [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 development of vaccines against the herpesviruses has major public health importance because of the wide spectrum of associated clinical disease with this virus in both immunocompetent and immunocompromised populations. Because these viruses establish latent infections capable of subsequent reactivation, both immunotherapeutic and prophylactic vaccine strategies are needed. A range of vaccine formulations has been devised, largely as a result of the rapid growth in knowledge in molecular microbiology and genetic engineering, including live and inactivated whole virus vaccines, and subunit vaccines consisting of recombinant viral glycoproteins in various adjuvants. The live attenuated virus Oka strain vaccine is now licensed for prophylaxis against varicella (VZV) in some countries. Recent studies with herpes simplex viruses (HSV) have demonstrated immunogenicity with glycoprotein vaccines; however, these studies have also highlighted their failure to reduce seroconversion to HSV-2 in high-risk populations. Nevertheless, his work has helped develop comprehensive methodologies for the clinical amd immunological assessment of newer vaccine formulations which have proved successful in animal models. The live attenuated Towne strain vaccine has been shown to prevent severe human cytomegalovirus (CMV) infection in transplant recipients. More recently, subunit antigens and virus vector vaccines against CMV and Epstein Barr virus (EBV) have been devised. Novel attempts to present viral antigens now include the development of plasmid expression vectors for viral nucleic acids and genes as well as engineered live vectors for viral antigens. These new technologies may allow future vaccines to be devised, not only against the 5 well characterised herpes viruses, but also against the recently recognised herpes viruses 6, 7 and 8 whose full clinical spectrum is still unknown. [ABSTRACT FROM AUTHOR]

Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of turkeys (HVT) has been successfully developed and used as a recombinant vaccine vector to induce protection against other avian viral diseases such as infectious bursal disease (IBD), Newcastle disease (ND) or avian influenza (AI). Although effective when administered individually, recombinant HVT vectors have limitations when combined in multivalent vaccines. Thus there is a need for developing additional viral vectors that could be combined with HVT in inducing protection against multiple avian diseases in multivalent vaccines. Gallid herpesvirus 3 (GaHV3) strain SB-1 is widely used by the poultry industry as bivalent vaccine in combination with HVT to exploit synergistic effects against MD. Here, we report the development and application of SB-1 as a vaccine vector to express the VP2 capsid antigen of IBD virus. A VP2 expression cassette was introduced into the SB-1 genome at three intergenic locations (UL3/UL4, UL10/UL11 and UL21/UL22) using recombineering methods on the full-length pSB-1 infectious clone of the virus. We show that the recombinant SB-1 vectors expressing VP2 induced neutralising antibody responses at levels comparable to that of commercial HVT-based VAXXITEKHVT+IBD vaccine. Birds vaccinated with the experimental recombinant SB-1 vaccine were protected against clinical disease after challenge with the very virulent UK661 IBDV isolate, demonstrating its value as an efficient viral vector for developing multivalent vaccines against avian diseases. Veterinary medicine: an effective vaccine platform to overcome multiviral interference Gallid herpesvirus 3 (GaHV3) strain SB-1 is effective in delivering vaccine material to cells, overcoming a major roadblock in poultry vaccination. UK researchers, led by the Prof. Venugopal Nair OBE at the Pirbright Institute, have constructed a vaccine against Marek's disease virus (MDV) and infectious bursal disease viruses (IBDV). Both MDV and IBDV are deadly viruses of poultry industry. For this purpose, GaHV3 strain SB-1 (a vaccine strain of virus against MDV) was used and genetic materials for VP2 (one of the surface glycoproteins of IBDV) was incorporated into the genome of SB-1. Cells inoculated with the viral vaccine produce the VP2 proteins of IBDV which then primes a host's immune system response against infection. Birds immunized with the team's vaccine remained free of clinical symptoms after IBDV infection, highlighting the potential of SB-1 to be used as a vector against other avian diseases. The use of SB-1 also sidesteps a constraint of previous vaccines, based on herpesvirus of turkeys (HVT), which is recommended not to be combined with other HVT based vaccines. SB-1 vaccines can be administered alongside HVT vaccines and they can provide a better immunity against MDV, highlighting the potential of SB-1 to be used as a vector against other avian vidal diseases. [ABSTRACT FROM AUTHOR]