BIOLOGICAL SIGNIFICANCE: Laticauda colubrina (yellow-lipped sea krait) is a widely distributed, semi-aquatic venomous snake species. The venom proteome at the level of protein family is unsophisticated and consistent with its restricted prey selection. Nonetheless, the subproteomic findings revealed geographical variability of the venom for this widely distributed species. In contrast to two previous reports, the results for the Balinese L. colubrina venom showed that LNTX Neurotoxin a and Neurotoxin b were co-existent while the PLA2 lethal subtype (PLA-II) was undetected by means of LCMS/MS and by in vivo assay. This is an observable trait of L. colubrina considered divergent from specimens previously studied for the Philippines and the Solomon Islands. The stark geographical variation might be reflective of trophic adaptation following evolutionary arms race between the snake and the prey (eels) in different localities. The preferred trait would likely propagate and remain significant within the geographical population, since the strong behaviour of site fidelity in the species would have minimized gene flow between distant populations. Meanwhile, the in vivo neutralization study verified that the efficacy of the heterologous Sea Snake Antivenom (Australian product) is attributable to the cross-neutralization of SNTX and LNTX, two principal lethal toxins that made up the bulk of L. colubrina venom proteins. The findings also implied that L. colubrina, though could be evolutionarily more related to the terrestrial elapids, has evolved a much streamlined, neurotoxin- and PLA2-predominated venom arsenal, with major antigenicity shared among the true sea snakes and the Australo-Papuan elapids. The findings enrich our current understanding of the complexity of L. colubrina venom and the neutralizing spectrum of antivenom against the principal toxins from this unique elapid lineage.
METHODS: A systematic literature search with no language restriction was performed in electronic databases and preprint repositories to identify eligible studies published up to 29 June 2021. The outcomes of interest were hospital admission and all-cause mortality. A random-effects model was used to estimate the pooled odds ratio (OR) for outcomes of interest with the use of neutralizing monoclonal antibodies relative to nonuse of neutralizing monoclonal antibodies, at 95% confidence intervals (CI).
RESULTS: Our systematic literature search identified nine randomized controlled trials. Three trials had an overall low risk of bias, while four trials had some concerns in the overall risk of bias. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.69; 95% CI 0.33-1.47), but a statistically significant reduction in the odds of hospital admission (pooled OR = 0.29; 95% CI 0.21-0.42), with the administration of a neutralizing monoclonal antibody among patients with COVID-19, relative to non-administration of a neutralizing monoclonal antibody, at the current sample size.
CONCLUSION: The reduced risk of hospital admission with neutralizing monoclonal antibodies use suggests that the timing of neutralizing antibodies administration is key in preventing hospital admission and, ultimately, death. Future randomized trials should aim to determine if the clinical outcomes with neutralizing monoclonal antibodies differ based on serostatus.
METHODS: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies.
RESULTS: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection.
CONCLUSIONS: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management.
METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1.
CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.
METHODS: We systematically searched five electronic databases (PubMed, CENTRAL, Embase, Global Health, and PsycINFO) from date of inception to September 30, 2022, for studies reporting on the effect of bebtelovimab in SARS-CoV-2 infection, using a combination of search terms around -bebtelovimab‖, -LY-CoV1404‖, -LY3853113‖, and -coronavirus infection‖. All citations were screened independently by two researchers. Data were extracted and thematically analyzed based on study design by adhering to the stipulated scoping review approaches.
RESULTS: Thirty-nine studies were included, thirty-four non-clinical studies were narratively synthesized, and five clinical studies were meta-analyzed. The non-clinical studies revealed bebtelovimab not only potently neutralized wide-type SARS-CoV-2 and existing variants of concern such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but also retained appreciable activity against Omicron lineages, including BA.2.75, BA.4, BA.4.6, and BA.5. Unlike other monoclonal antibodies, bebtelovimab was able to bind to epitope of the SARS-CoV-2 S protein by exploiting loop mobility or by minimizing side-chain interactions. Pooled analysis from clinical studies depicted that the rates of hospitalization, ICU admission, and death were similar between bebtelovimab and other COVID-19 therapies. Bebtelovimab was associated with a low incidence of treatment-emergent adverse events.
CONCLUSION: Preclinical evidence suggests bebtelovimab be a potential treatment for COVID-19 amidst viral evolution. Bebtelovimab has comparable efficacy to other COVID-19 therapies without evident safety concerns.