tetano
Editor, Senior Moderator
J Virol. 2014 Sep 10. pii: JVI.01532-14. [Epub ahead of print]
Broad Protection against Avian Influenza using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin gene.
Kamlangdee A1, Kingstad-Bakke B1, Anderson TK2, Goldberg TL1, Osorio JE3.
Author information
Abstract
A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza strains diverge by 1-2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant Modified Vaccinia Ankara (MVA) virus that expresses an H5N1 mosaic hemagglutinin (H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clades 0, 1 and 2 avian influenza viruses and also protected against seasonal H1N1 virus (PR8). It also provided short- (10 days) and long-term (6 months) protection post-vaccination. Both neutralizing antibodies and antigen-specific CD4+ and CD8+ T cells were still detected after 5 months post-vaccination suggesting long-lasting immunity.
IMPORTANCE:
Influenza viruses infect a billion people every year and cause up to 500,000 deaths. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel in silico mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as inducing broader immunity than a wild-type hemagglutinin.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25210173
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25210173
Broad Protection against Avian Influenza using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin gene.
Kamlangdee A1, Kingstad-Bakke B1, Anderson TK2, Goldberg TL1, Osorio JE3.
Author information
Abstract
A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza strains diverge by 1-2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant Modified Vaccinia Ankara (MVA) virus that expresses an H5N1 mosaic hemagglutinin (H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clades 0, 1 and 2 avian influenza viruses and also protected against seasonal H1N1 virus (PR8). It also provided short- (10 days) and long-term (6 months) protection post-vaccination. Both neutralizing antibodies and antigen-specific CD4+ and CD8+ T cells were still detected after 5 months post-vaccination suggesting long-lasting immunity.
IMPORTANCE:
Influenza viruses infect a billion people every year and cause up to 500,000 deaths. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel in silico mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as inducing broader immunity than a wild-type hemagglutinin.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25210173
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25210173