Immune responses against recombinant poxvirus vaccines that express full-length lyssavirus glycoprotein genes

Rabies is a fatal but preventable neurotropic disease of potentially all mammals. The disease is caused by lyssaviruses. Rabies is recognized as the 10th most common lethal infectious disease in the world, rendering it one of the most feared zoonotic diseases known to man. Nevertheless, rabies can be prevented by application of pre- or post exposure treatments. Rabies vaccines have been available since the time of Pasteur, more that one hundred years ago. Since, vaccine research focused on the development of safer and more effective vaccines. Topics of current interest in the field of rabies vaccinology were addressed in this study. A primary concern regarding the disease is human mortalities, in the range of 60 000, reported every year. Most of these are linked to exposure to rabid dogs. In addition, a great number of post exposure treatments are administered each year at great costs. Despite availability of efficacious biologics, several factors influence the optimal use and accessibility of these agents in the countries of interest, with cost and availability being the major contributing factors. A proven approach is mass oral vaccination of target animals, such as dogs, which indirectly infers protection to susceptible hosts, including man. Currently available vaccines present several disadvantages of use though, including issues of safety or doubtful stability. Safer but effective alternative vaccines that could be used in oral baits would be valuable. Here the use of two candidate host restricted poxvirus vaccine vectors were explored, particularly also in regard to oral innocuity. The construction, convenient isolation and use of a recombinant Lumpy skin disease virus (Neethling strain) expressing rabies virus glycoprotein in a mouse model were investigated. In addition, a recombinant Modified Vaccinia virus Ankara expressing rabies virus glycoprotein was prepared and tested as a vaccine in mice, dogs and raccoons. In both cases it was clear that the severe attenuation of these viruses did affect the efficacy of the recombinant vaccines in the non-permissive hosts. With the recombinant MVA a clear dosage effect could be shown, and equivalent humoral responses could only be attained at much higher titers of vaccine virus as with replication competent counterparts. Secondly, the cross-protection of rabies vaccines across the spectrum of lyssaviruses was addressed. Lyssaviruses can be divided into two groups based on sequence analysis and pathogenesis. Viruses belonging to the so-called phylogroup II, are the Mokola, Lagos and West Caucasian Bat viruses. Classic rabies biologics fail to fully protect against the viruses attributed to a lack of cross-neutralization. Here, cross-protection and cross-reactive immune responses induced by recombinant vaccinia viruses expressing rabies, Mokola or West Caucasian Bat virus glycoproteins, in single or dual combinations, were investigated. As expected, there was a lack of cross-protection of rabies and Mokola glycoprotein vaccines. There was also a clear lack of cross-protection of West Caucasian Bat virus glycoprotein vaccine and rabies and Mokola viruses. The dual antigen expressing vaccines did not appear to offer any additional protective effect in the tested model. The Mokola virus glycoprotein vaccines induced neutralizing antibody responses that significantly cross-neutralized Lagos Bat virus.Thesis (PhD (Microbiology))--University of Pretoria, 2006.Microbiology and Plant Pathologyunrestricte

Coding-complete genome of human alphaherpesvirus 1 isolated from a case of fulminant hepatitis

DATA AVAILABILITY : This sequence has been deposited in GenBank under the accession number OQ102003.1 (https://www.ncbi.nlm.nih.gov/nuccore/OQ102003.1). The version described here is the first version. The raw reads were deposited in the NCBI Sequence Read Archive (SRA) under the accession number PRJNA913943 (https://www.ncbi.nlm.nih.gov/sra/SRX18774967 and https://www.ncbi.nlm.nih.gov/sra/SRX18774968).We report the coding-complete genome sequence of human alphaherpesvirus 1 (HHV1) isolated from a previously healthy 64-year-old male with fulminant hepatitis, a rare presentation of a common viral agent. The sequence is highly similar to previously described HHV1 sequences. Additional sequence data for fulminant hepatitis cases are required.The National Research Foundation (NRF) of South Africa, the NRF South African Research Chairs Initiative and operational funding at the NICD/NHLS.https://journals.asm.org/journal/mraam2024Medical VirologySDG-03:Good heatlh and well-bein

A rabies-related lyssavirus from a Nycticeinops schlieffeni bat with neurological signs, South Africa

DATA AVAILABILITY: The phala bat Lyssavirus sequence has been deposited in GenBank under the accession number OQ970171. The version described in this paper is the first version. Raw reads were deposited in the NCBI Sequence Read Archive available at PRJNA971078 under the accession numbers PRJNA971078 (BioProject) and SAMN35019052 (BioSample). The sequence data used for bat identification have been deposited in GenBank under the accession numbers OR096071 (12s rRNA gene) OR091287 (COI gene) and OR105696 (Cytb gene).We report the coding-complete sequence of a lyssavirus, provisionally designated Phala bat lyssavirus (PBLV), characterized using a metagenomics approach. PBLV was identified in a Nycticeinops schlieffeni bat that exhibited neurological signs and died within 24 hours of admission to a wildlife rehabilitation center in Phalaborwa, South Africa.Funding was available from the South African Research Chair Initiative of the Department of Science and Innovation and was administered by the National Research Foundation of South Africa and operational funding utilized for NGS. Postdoctoral fellowship funding provided by the University of Pretoria (UP), under the UP Co-Funding Postdoctoral Fellowship Programme.https://journals.asm.org/journal/mraMedical VirologySDG-03:Good heatlh and well-bein

Reverse transcription recombinase polymerase amplification assay for rapid detection of canine associated rabies virus in Africa

Rabies is a neglected disease mostly affecting the developing world. Accurate and reliable diagnostic and surveillance data forms the foundation for the formulation and monitoring of control strategies. Although various sensitive and specific tests are available for detection of rabies virus, implementation of these tests in low-resource settings are challenging and remains limited. In this study, we describe the developed of a reverse transcription recombinase polymerase amplification assay for the detection of rabies virus. The analytical sensitivity of this assay was determined to be 562 RNA copies and was performed in 20 minutes. The diagnostic sensitivity of the RT-RPA was 100% for detection of rabies virus in field samples. In conclusion, the RT-RPA assay allowed for very quick and sensitive detection of rabies virus and could be adapted for use in low-source settings.Supporting information: S1 Table. Details of rabies virus sequences used for primer and probe design for the RT-RPA assay.S2 Table. Evaluation of the mismatches between the RT-RPA primer and probe set binding regions to rabies-related lyssaviruses.The South African Research Chair initiative of the Department of Science and Technology and National Research Foundation of South Africa and the Poliomyelitis Research Foundation.http://www.plosone.orgpm2020BiochemistryGeneticsMedical VirologyMicrobiology and Plant Patholog

Development of a Pan-Filoviridae SYBR green qPCR assay for biosurveillance studies in bats

DATA AVAILABILITY: The data are contained within the article or supplementary materials.SUPPLEMENTARY MATERIALS : TABLE S1: Publically available sequences used for primer design; SUPPLEMENTARY FILE S1: Synthetic constructs sequences, TABLE S2: SYBR Green qPCR results for field samples.Recent studies have indicated that bats are hosts to diverse filoviruses. Currently, no panfilovirus molecular assays are available that have been evaluated for the detection of all mammalian filoviruses. In this study, a two-step pan-filovirus SYBR Green real-time PCR assay targeting the nucleoprotein gene was developed for filovirus surveillance in bats. Synthetic constructs were designed as representatives of nine filovirus species and used to evaluate the assay. This assay detected all synthetic constructs included with an analytical sensitivity of 3–31.7 copies/reaction and was evaluated against the field collected samples. The assay’s performance was similar to a previously published probe based assay for detecting Ebola- and Marburgvirus. The developed pan-filovirus SYBR Green assay will allow for more affordable and sensitive detection of mammalian filoviruses in bat samples.National Research Foundation (NRF) of South Africa.https://www.mdpi.com/journal/virusesMedical Virolog

Overview of bat and wildlife coronavirus surveillance in Africa : a framework for global investigations

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had devastating health and socio-economic impacts. Human activities, especially at the wildlife interphase, are at the core of forces driving the emergence of new viral agents. Global surveillance activities have identified bats as the natural hosts of diverse coronaviruses, with other domestic and wildlife animal species possibly acting as intermediate or spillover hosts. The African continent is confronted by several factors that challenge prevention and response to novel disease emergences, such as high species diversity, inadequate health systems, and drastic social and ecosystem changes. We reviewed published animal coronavirus surveillance studies conducted in Africa, specifically summarizing surveillance approaches, species numbers tested, and findings. Far more surveillance has been initiated among bat populations than other wildlife and domestic animals, with nearly 26,000 bat individuals tested. Though coronaviruses have been identified from approximately 7% of the total bats tested, surveillance among other animals identified coronaviruses in less than 1%. In addition to a large undescribed diversity, sequences related to four of the seven human coronaviruses have been reported from African bats. The review highlights research gaps and the disparity in surveillance efforts between different animal groups (particularly potential spillover hosts) and concludes with proposed strategies for improved future biosurveillance.The National Research Foundation (NRF) of South Africa: the DSI-NRF South African Research Chair fellowship funding; the Department of the Defense, Defense Threat Reduction Agency and the University of Pretoria’s postdoctoral funding program.http://www.mdpi.com/journal/virusespm2021Medical Virolog

Now is the time to set up formal forums for clinical advice with emerging and zoonotic infections : a shared experience

No abstract available.https://www.elsevier.com/locate/tmaidhj2024Medical VirologySDG-03:Good heatlh and well-bein

Rift Valley fever virus seroprevalence among humans, Northern KwaZulu-Natal Province, South Africa, 2018-2019

We detected Rift Valley fever virus (RVFV) IgM and IgG in human serum samples collected during 2018–2019 in northern KwaZulu-Natal Province, South Africa. Our results show recent RVFV circulation and likely RVFV endemicity in this tropical coastal plain region of South Africa in the absence of apparent clinical disease.The Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases, US Centers for Disease Control and Prevention Division .http://www.cdc.gov/eidam2022Medical Virolog