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Order Martellivirales: Togaviridae
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Next, a tetravalent VEEV-vector-based dengue (White et al. 2007, 2013; Khalil et al. 2014a) was elaborated. Then, the putative Lassa virus (LASV) vaccines were successfully developed. First, the wild-type LASV glycoprotein (GPCwt) and a noncleavable C-terminally deleted modification (ΔGPfib) were expressed from individual VEE 26S subgenomic promoters and demonstrated high immunogenicity and protectivity in mice (Wang M et al. 2018). The VEE sriVLPs were also applied for expression of GPCs of Junin (JUNV) and Machupo (MACV) viruses and elicited humoral immune responses, which correlated with complete protection against challenges with JUNV and MACV, respectively (Johnson et al. 2020).
Viral Hemorrhagic Fevers: Laboratory Diagnosis
Published in James H. S. Gear, CRC Handbook of Viral and Rickettsial Hemorrhagic Fevers, 2019
Several Lassa-related arenaviruses have been discovered in Africa, including Mopeia from Mozambique70 and Mobala71 and Ippy72 viruses from the Central African Republic. To date, only the West African Lassa virus has been associated with hemorrhagic fever in man. The IFA test is the most rapid test available for serological diagnosis of Lassa fever, both IgM and G antibodies being detectable in serum between the 6th and 14th day after disease onset.35,73-74 Antibodies to members of the African arenavirus complex cross-react markedly by IFA test, but because of the restricted geographical area of Lassa fever infection, this is unlikely to present problems in serological diagnosis. Reversed passive hemagglutination inhibition (RPHI)75 and a recently described ELISA test74,76 appear to be of a similar sensitivity to the IFA test. In contrast, CF antibodies are low titered and their appearance is often delayed until days 15 to 28 after onset of symptoms.73,77
Pathogens Causing Multisystem Infections
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
Lassa virus causes an often fatal disease transmitted to humans by contact with persistently infected rodents in West and Central Africa. The laboratory diagnosis is usually accomplished by cell culture. A combination of reverse transcription of the Lassa virus RNA sequences followed by PCR works on blood and urine specimens, offering a rapid, alternative method of diagnosis for this dangerous systemic infection.
Patent landscape of novel technologies for combating category-A Arenavirus infections
Published in Expert Opinion on Therapeutic Patents, 2020
Harshal Sudhakar, Jignesh Bhate, Asish Kumar Patra
CN105296507A [53] discloses Lassa fever virus like particles. The nucleic acids coding various Lassa fever proteins were cloned into Baculovirus vector and expressed in insect cell line. The virus like particles thus formed were isolated and purified and administered to healthy BALB/c mice, the antibody titers thus formed were measured by ELISpot assay. Antibody neutralization activity was measured using immunized mice serum, VLP were found to be more immunogenic if administered along with adjuvant. 10357562 USDB2 [54] discloses monoclonal antibody against glycoprotein of Lassa virus. Human origin Mab is IgG class, was tested in guinea pigs. LASV Josiah challenged guinea pigs were administered via intra-peritoneal route with two monoclonal antibodies MAb GP19.7E and MAb GP10.4B at 30 mg/Kg and 15 mg/Kg, respectively. The animals were monitored for diseases symptoms, control animals showed typical signs of Lassa virus infection and succumbed by day16 post-infection; whereas Mab treated animals did not show any symptoms of Lassa virus infection. The antibodies provided complete protection and prolonged the survival. The antibodies were isolated from peripheral blood mononuclear cells (PBMC) obtained from convalescence blood.
Post-exposure prophylactic vaccine candidates for the treatment of human Risk Group 4 pathogen infections
Published in Expert Review of Vaccines, 2020
James Logue, Ian Crozier, Peter B Jahrling, Jens H Kuhn
Lassa virus (LASV; Arenaviridae: Mammarenavirus), responsible for an estimated 300,000 to 500,000 cases of Lassa fever annually, is predominantly endemic in Guinea, Liberia, Nigeria, and Sierra Leone [107]. Symptoms and clinical signs of Lassa fever include fever, nausea, muscle aches, and in severe cases, hemorrhage, multi-system organ dysfunction, and death. LASV is most commonly transmitted through contact with infected rodents (predominantly Natal mastomys [Mastomys natalensis Smith, 1834]) or excrement from these rodents, but person-to-person transmission is limited. Vaccine development to prevent Lassa fever has been severely hampered by the high-genetic diversity associated with the multitude of LASV isolates [108]. However, with this caveat, a vaccine composed of single-cycle LASV replicating particles (VRPs) was 100% (5 of 5) efficacious when administered 24 h subsequent to an otherwise lethal LASV Josiah strain exposure in strain 13 guinea pigs [109]. Additionally, a recombinant vaccine, DEF201, has shown PEP efficacy against ‘arenaviral hemorrhagic fever’ in a Pichindé virus golden hamster surrogate model for Lassa fever, but efficacy against other mammarenaviruses, including LASV, is lacking [110]. At this time, no PEP vaccine testing in NHPs infected with LASV has been reported.
Recent advances in the development and evaluation of molecular diagnostics for Ebola virus disease
Published in Expert Review of Molecular Diagnostics, 2019
John Tembo, Edgar Simulundu, Katendi Changula, Dale Handley, Matthew Gilbert, Moses Chilufya, Danny Asogun, Rashid Ansumana, Nathan Kapata, Francine Ntoumi, Giuseppe Ippolito, Alimuddin Zumla, Matthew Bates
Another interesting consideration from a diagnostic perspective is the existence of IgG seropositive asymptomatic case contacts and other healthy blood donors who have no history of severe Ebola-like disease. A study of case contacts in Sierra Leone reported Ebola IgG seroprevalence at 11% [24]. In a recent study from Boende Health Zone in the DRC (site of the 2014 EVD outbreak) a range of serological tests were used to screen 565 health workers (not restricted to case contacts), among whom 234 (41.4%) were seroreactive to at least one EBOV protein [25]. Among these cases, sera from a small minority (16) could neutralize a recombinant HIV virus expressing EBOV glycoprotein (GP). It is now widely accepted that in a minority of cases EBOV can cause a mild, sub-clinical or asymptomatic but replicative infection [26,27]. Epidemiologically it is difficult to argue that this accounts for seroprevalence rates observed in healthy populations with no history of EVD disease or case-contact, data from the DRC suggest EBOV IgG seroprevalence rates of 11% among the general population [28] and up to 18% among Efe pigmy populations [29]. In Sierra Leone, a retrospective biobank study of patients with suspected Lassa virus (LASV) infection (but who were LASV IgM and malaria negative) found low titer Ebola IgM in 8.6% of all cases [30]. Other non-mutually exclusive theoretical explanations for population-level seroprevalence could include the idea that the EBOV antigens used could be cross-reacting with antibodies from novel/unknown filovirus species that cause only mild or sub-clinical infection, the idea that there could be cross-reactivity with homologous proteins of other viruses such as the GP proteins of arenaviruses or bunyaviruses [31] or simply unrelated non-specific binding/noise due to issues with assay use or design and validation.