tetano
Editor, Senior Moderator
J Virol. 2016 May 18. pii: JVI.00730-16. [Epub ahead of print]
[h=1]Mosaic H5 hemagglutinin provides broad humoral and cellular immune responses against influenza viruses.[/h] Kamlangdee A[SUP]1[/SUP], Kingstad-Bakke B[SUP]1[/SUP], Osorio JE[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The most effective way to prevent influenza infection is via vaccination. However, the constant mutation of influenza viruses due to antigenic drift and shift compromises vaccine efficacy. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. Using the modified vaccinia Ankara (MVA) virus, we had previously generated a recombinant vaccine against highly pathogenic avian influenza (H5N1) based on an in silico mosaic approach. This MVA-H5M construct protected mice against multiple clades of H5N1 and H1N1 viruses. We have now further characterized the immune responses using immune-depletion of T cells and passive serum transfer, and these studies indicate that antibodies are the main contributors in homosubtypic protection (H5N1 clades). When compared with a MVA construct expressing HA from influenza A/VN/1203/04, MVA-HA), the MVA-H5M vaccine markedly increased and broadened B cell and T cell responses against H5N1 virus. The MVA-H5M also provided effective protection with no morbidity against H5N1 challenge; whereas, MVA-HA vaccinated mice showed clinical signs and experienced significant weight loss. In addition, MVA-H5M induced CD8[SUP]+[/SUP] T cell responses that play a major role in heterosubtypic protection (H1N1). Finally, expression of the H5M gene as either a DNA vaccine or subunit protein protected mice against H5N1 challenge, indicating the effectiveness of the mosaic sequence without viral vectors for the development of a universal influenza vaccine.
[h=4]IMPORTANCE:[/h] Influenza viruses infect up to one billion people around the globe each year and are responsible for 300,000-500,000 deaths annually. Vaccines are still the main intervention to prevent infection but they fail to provide effective protection against heterologous strains of viruses. We developed broadly reactive H5N1 vaccine based on an in silico mosaic approach and previously demonstrated that modified vaccinia Ankara expressing an H5 mosaic hemagglutinin prevented infection with multiple clades of H5N1 and limited severe disease after H1N1 infection. Further characterization revealed that antibody responses and T cells are main contributors to protection against H5N1 and H1N1 viruses, respectively. The vaccine also broadens both T cell and B cell responses compared to native H5 vaccine from influenza A/Vietnam/1203/04. Finally, delivering the H5 mosaic as a DNA vaccine or as a purified protein demonstrated effective protection similar to the viral vector approach.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27194759 [PubMed - as supplied by publisher]
[h=1]Mosaic H5 hemagglutinin provides broad humoral and cellular immune responses against influenza viruses.[/h] Kamlangdee A[SUP]1[/SUP], Kingstad-Bakke B[SUP]1[/SUP], Osorio JE[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The most effective way to prevent influenza infection is via vaccination. However, the constant mutation of influenza viruses due to antigenic drift and shift compromises vaccine efficacy. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. Using the modified vaccinia Ankara (MVA) virus, we had previously generated a recombinant vaccine against highly pathogenic avian influenza (H5N1) based on an in silico mosaic approach. This MVA-H5M construct protected mice against multiple clades of H5N1 and H1N1 viruses. We have now further characterized the immune responses using immune-depletion of T cells and passive serum transfer, and these studies indicate that antibodies are the main contributors in homosubtypic protection (H5N1 clades). When compared with a MVA construct expressing HA from influenza A/VN/1203/04, MVA-HA), the MVA-H5M vaccine markedly increased and broadened B cell and T cell responses against H5N1 virus. The MVA-H5M also provided effective protection with no morbidity against H5N1 challenge; whereas, MVA-HA vaccinated mice showed clinical signs and experienced significant weight loss. In addition, MVA-H5M induced CD8[SUP]+[/SUP] T cell responses that play a major role in heterosubtypic protection (H1N1). Finally, expression of the H5M gene as either a DNA vaccine or subunit protein protected mice against H5N1 challenge, indicating the effectiveness of the mosaic sequence without viral vectors for the development of a universal influenza vaccine.
[h=4]IMPORTANCE:[/h] Influenza viruses infect up to one billion people around the globe each year and are responsible for 300,000-500,000 deaths annually. Vaccines are still the main intervention to prevent infection but they fail to provide effective protection against heterologous strains of viruses. We developed broadly reactive H5N1 vaccine based on an in silico mosaic approach and previously demonstrated that modified vaccinia Ankara expressing an H5 mosaic hemagglutinin prevented infection with multiple clades of H5N1 and limited severe disease after H1N1 infection. Further characterization revealed that antibody responses and T cells are main contributors to protection against H5N1 and H1N1 viruses, respectively. The vaccine also broadens both T cell and B cell responses compared to native H5 vaccine from influenza A/Vietnam/1203/04. Finally, delivering the H5 mosaic as a DNA vaccine or as a purified protein demonstrated effective protection similar to the viral vector approach.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27194759 [PubMed - as supplied by publisher]