Live-attenuated H1N1 influenza vaccine candidate displays potent efficacy in mice and ferrets

Autor: Steffen Mueller, Anna Kushnir, J. Robert Coleman, Chen Yang, Chiahsuan Chin, David Boltz, Charles B. Stauft
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
RNA viruses
Viral Diseases
Physiology
viruses
Hemagglutinin Glycoproteins
Influenza Virus
medicine.disease_cause
Biochemistry
Mice
0302 clinical medicine
Influenza A Virus
H1N1 Subtype
Immune Physiology
Influenza A virus
Medicine and Health Sciences
Live attenuated influenza vaccine
Public and Occupational Health
030212 general & internal medicine
Pathology and laboratory medicine
Mammals
Vaccines
Mice
Inbred BALB C
Multidisciplinary
Attenuated vaccine
Immune System Proteins
biology
Viral Vaccine
H1N1
Vaccination
virus diseases
Eukaryota
Medical microbiology
Vaccination and Immunization
3. Good health
Infectious Diseases
Influenza Vaccines
Mice
Inbred DBA
Vertebrates
Viruses
Medicine
Computer-Aided Design
Pathogens
Research Article
Infectious Disease Control
Influenza vaccine
Science
Immunology
Neuraminidase
Vaccines
Attenuated
Microbiology
Antibodies
03 medical and health sciences
Viral Proteins
Virology
medicine
Animals
Influenza viruses
Antigens
business.industry
Organisms
Ferrets
Viral pathogens
Biology and Life Sciences
Proteins
Viral Vaccines
Influenza
Microbial pathogens
Disease Models
Animal
030104 developmental biology
Inactivated vaccine
Amniotes
biology.protein
Preventive Medicine
business
Orthomyxoviruses
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 10, p e0223784 (2019)
ISSN: 1932-6203
Popis: Currently, influenza vaccine manufacturers need to produce 1-5 x 107 PFU of each vaccine strain to fill one dose of the current live-attenuated-influenza-vaccine (LAIV). To make a single dose of inactivated vaccine (15 ug of each hemagglutinin), the equivalent of 1010 PFU of each vaccine strains need to be grown. This high dose requirement is a major drawback for manufacturing as well as rapidly sourcing sufficient doses during a pandemic. Using our computer-aided vaccine platform Synthetic Attenuated Virus Engineering (SAVE), we created a vaccine candidate against pandemic H1N1 A/CA/07/2009 (CodaVax-H1N1) with robust efficacy in mice and ferrets, and is protective at a much lower dose than the current LAIV. CodaVax-H1N1 is currently in Phase I/II clinical trials. The hemagglutinin (HA) and neuraminidase (NA) gene segments of A/California/07/2009 (H1N1) (CA07) were "de-optimized" and a LAIV was generated ex silico using DNA synthesis. In DBA/2 mice, vaccination at a very low dose (100 or approximately 1 PFU) with CodaVax-H1N1 prevented disease after lethal challenge with wild-type H1N1. In BALB/c mice, as little as 103 PFU was protective against lethal challenge with mouse-adapted H1N1. In ferrets, CodaVax-H1N1 was more potent compared to currently licensed LAIV and still effective at a low dose of 103 PFU at preventing replication of challenge virus.
Databáze: OpenAIRE
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