Publications by authors named "J H Nunberg"
Article Synopsis
- Live-attenuated virus vaccines like Candid#1 aim to protect against diseases (e.g., Argentine hemorrhagic fever) but have risks of reverting to a more pathogenic form due to genetic mutations.
- In studies with mutant strains (I427F and A168T+I427F rCan), researchers found that while some mutations increased virulence in mice, others showed only modest effects, indicating a complex relationship between genetic changes and vaccine safety.
- To ensure the safety of future Candid#1 vaccines, it's crucial to stabilize key genetic mutations to prevent reversion to virulent strains.
Many enveloped viruses enter host cells by fusing with acidic endosomes. The fusion activity of multiple viral envelope glycoproteins does not generally affect viral membrane permeability. However, fusion induced by the Lassa virus (LASV) glycoprotein complex (GPc) is always preceded by an increase in viral membrane permeability and the ensuing acidification of the virion interior.
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- Live-attenuated virus vaccines, like the Candid#1 strain for Junín virus (JUNV), are effective but pose risks of reverting to a pathogenic form, which has led to their lack of approval in the U.S.
- A study found that a modified version of Candid#1, known as K33S rCan, is safe for guinea pigs, generates strong immune responses, and protects against lethal JUNV infections.
- Genetic analysis showed that K33S rCan does not revert to virulence in neonatal mice, indicating its potential as a safe second-generation vaccine for JUNV.
Old World (Africa) and New World (South America) arenaviruses are associated with human hemorrhagic fevers. Efforts to develop small molecule therapeutics have yielded several chemical series including the 4-acyl-1,6-dialkylpiperazin-2-ones. Herein, we describe an extensive exploration of this chemotype.
View Article and Find Full Text PDFThe Candid#1 strain of Junín virus was developed using a conventional attenuation strategy of serial passage in nonhost animals and cultured cells. The live-attenuated Candid#1 vaccine is used in Argentina to protect at-risk individuals against Argentine hemorrhagic fever, but it has not been licensed in the United States. Recent studies have revealed that Candid#1 attenuation is entirely dependent on a phenylalanine-to-isoleucine substitution at position 427 in the fusion subunit (GP2) of the viral envelope glycoprotein complex (GPC), thereby raising concerns regarding the potential for reversion to virulence.
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