Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region

Autor: Xinming Tu, Christopher E. Yi, Michael Farzan, Agegnehu Gettie, Lei Ba, Chuan Qin, Wenjie Yu, Zhiwei Chen, Tian He, David D. Ho, Linqi Zhang, Fengwen Zhang, Kwok-Yung Yuen, Jian Yu, Qiang Wei, Hong Gao
Jazyk: angličtina
Rok vydání: 2005
Předmět:
SARS Virus - genetics - immunology
Genes
Viral
viruses
Genetic Vectors
Immunology
Vaccinia virus
Carboxypeptidases
Peptidyl-Dipeptidase A
Antibodies
Viral
medicine.disease_cause
Recombinant virus
Microbiology
Virus
chemistry.chemical_compound
Viral Envelope Proteins
Neutralization Tests
Virology
Vaccines and Antiviral Agents
medicine
Vaccinia virus - genetics
Animals
Coronaviridae
Orthopoxvirus
Neutralizing antibody
Membrane Glycoproteins - chemistry - genetics - immunology
Antigens
Viral
Coronavirus
Recombination
Genetic
Membrane Glycoproteins
biology
Viral Vaccine
Viral Vaccines
biology.organism_classification
Macaca mulatta
Protein Structure
Tertiary
Antibodies
Viral - biosynthesis
Severe acute respiratory syndrome-related coronavirus
chemistry
Insect Science
Spike Glycoprotein
Coronavirus
biology.protein
Receptors
Virus
Viral Envelope Proteins - chemistry - genetics - immunology
Angiotensin-Converting Enzyme 2
Rabbits
Vaccinia
Epitope Mapping
Zdroj: Journal of Virology
Popis: Immunization with a killed or inactivated viral vaccine provides significant protection in animals against challenge with certain corresponding pathogenic coronaviruses (CoVs). However, the promise of this approach in humans is hampered by serious concerns over the risk of leaking live severe acute respiratory syndrome (SARS) viruses. In this study, we generated a SARS vaccine candidate by using the live-attenuated modified vaccinia virus Ankara (MVA) as a vector. The full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletion III region of the MVA genome. The newly generated recombinant MVA, ADS-MVA, is replication incompetent in mammalian cells and highly immunogenic in terms of inducing potent neutralizing antibodies in mice, rabbits, and monkeys. After two intramuscular vaccinations with ADS-MVA alone, the 50% inhibitory concentration in serum was achieved with reciprocal sera dilutions of more than 1,000- to 10,000-fold in these animals. Using fragmented S genes as immunogens, we also mapped a neutralizing epitope in the region of N-terminal 400 to 600 amino acids of the S glycoprotein (S400-600), which overlaps with the angiotensin-converting enzyme 2 (ACE2) receptor-binding region (RBR; S318-510). Moreover, using a recombinant soluble RBR-Fc protein, we were able to absorb and remove the majority of the neutralizing antibodies despite observing that the full S protein tends to induce a broader spectrum of neutralizing activities in comparison with fragmented S proteins. Our data suggest that a major mechanism for neutralizing SARS-CoV likely occurs through blocking the interaction between virus and the cellular receptor ACE2. In addition, ADS-MVA induced potent immune responses which very likely protected Chinese rhesus monkeys from pathogenic SARS-CoV challenge.
published_or_final_version
Databáze: OpenAIRE
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