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Complete Genome Sequences of Four African Horse Sickness Virus Strains from a Commercial Tetravalent Live Attenuated Vaccine.

ABSTRACT: This is a report of the complete genome sequences of plaque-selected isolates of each of the four virus strains included in a South African commercial tetravalent African horse sickness attenuated live virus vaccine.

SUBMITTER: Guthrie AJ

PROVIDER: S-EPMC4661309 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Complete Genome Sequences of Four African Horse Sickness Virus Strains from a Commercial Tetravalent Live Attenuated Vaccine.

Guthrie Alan J AJ Coetzee Peter P Martin Darren P DP Lourens Carina W CW Venter Estelle H EH Weyer Camilla T CT Joone Christopher C le Grange Misha M Harper Cindy K CK Howell Peter G PG MacLachlan N James NJ

Genome announcements 20151125 6

This is a report of the complete genome sequences of plaque-selected isolates of each of the four virus strains included in a South African commercial tetravalent African horse sickness attenuated live virus vaccine. ...[more]

PMID: 26607890

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Project description:UnlabelledThe causative agent of dengue fever, dengue virus (DENV), is transmitted by mosquitoes, and as distribution of these insects has expanded, so has dengue-related disease. DENV is a member of the Flaviviridae family and has 4 distinct serotypes (DENV-1, -2, -3, and -4). No lasting cross protection is afforded to heterologous serotypes following infection by any one of the individual serotypes. The presence of nonneutralizing antibodies to one serotype can facilitate the occurrence of more-severe dengue hemorrhagic fever through immune enhancement upon infection with a second serotype. For this reason, the development of a safe, tetravalent vaccine to produce a balanced immune response to all four serotypes is critical. We have developed a novel approach to produce safe and effective live-attenuated vaccines for DENV and other insect-borne viruses. Host range (HR) mutants of each DENV serotype were created by truncating transmembrane domain 1 of the E protein and selecting for strains of DENV that replicated well in insect cells but not mammalian cells. These vaccine strains were tested for immunogenicity in African green monkeys (AGMs). No vaccine-related adverse events occurred. The vaccine strains were confirmed to be attenuated in vivo by infectious center assay (ICA). Analysis by 50% plaque reduction neutralization test (PRNT50) established that by day 62 postvaccination, 100% of animals seroconverted to DENV-1, -2, -3, and -4. Additionally, the DENV HR tetravalent vaccine (HR-Tet) showed a tetravalent anamnestic immune response in 100% (16/16) of AGMs after challenge with wild-type (WT) DENV strains.ImportanceWe have generated a live attenuated viral (LAV) vaccine capable of eliciting a strong immune response in African green monkeys (AGMs) in a single dose. This vaccine is delivered by injecting one of four attenuated serotypes into each limb of the animal. 100% of animals given the vaccine generated antibodies against all 4 serotypes, and this response was found to be balanced in nature. This is also one of the first studies of dengue in AGMs, and our study suggests that viremia and antibody response in AGMs may be similar to those seen in DENV infection in humans.

Project description:BACKGROUND:African horse sickness (AHS) is a serious viral disease of equids resulting in the deaths of many equids in sub-Saharan Africa that has been recognized for centuries. This has significant economic impact on the horse industry, despite the good husbandry practices. Currently, prevention and control of the disease is based on administration of live attenuated vaccines and control of the arthropod vectors. RESULTS:A total of 29 horses in 2 groups, were vaccinated. Eighteen horses in Group 1 were further divided into 9 subgroups of 2 horses each, were individually immunised with one of 1 to 9 AHS serotypes, respectively. The eleven horses of Group 2 were immunised with all 9 serotypes simultaneously with 2 different vaccinations containing 5 serotypes (1, 4, 7-9) and 4 serotypes (2, 3, 5, 6) respectively. The duration of this study was 12?months. Blood samples were periodically withdrawn for serum antibody tests using ELISA and VNT and for 2?weeks after each vaccination for PCR and virus isolation. After the booster vaccination, these 27 horses seroconverted, however 2 horses responded poorly as measured by ELISA. In Group 1 ELISA and VN antibodies declined between 5 to 7?months post vaccination (pv). Twelve months later, the antibody levels in most of the horses decreased to the seronegative range until the annual booster where all horses again seroconverted strongly. In Group 2, ELISA antibodies were positive after the first booster and VN antibodies started to appear for some serotypes after primary vaccination. After booster vaccination, VN antibodies increased in a different pattern for each serotype. Antibodies remained high for 12?months and increased strongly after the annual booster in 78% of the horses. PCR and virus isolation results remained negative. CONCLUSIONS:Horses vaccinated with single serotypes need a booster after 6?months and simultaneously immunised horses after 12?months. Due to the non-availability of a facility in the UAE, no challenge infection could be carried out.

Dataset Information

Complete Genome Sequences of Four African Horse Sickness Virus Strains from a Commercial Tetravalent Live Attenuated Vaccine.

Publications

Complete Genome Sequences of Four African Horse Sickness Virus Strains from a Commercial Tetravalent Live Attenuated Vaccine.

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