Tweet
J Immunol. 2019 Aug 9. pii: ji1900819. doi: 10.4049/jimmunol.1900819. [Epub ahead of print]
A Novel Vaccine Strategy to Overcome Poor Immunogenicity of Avian Influenza Vaccines through Mobilization of Memory CD4 T Cells Established by Seasonal Influenza.
DiPiazza AT1, Fan S2, Rattan A1, DeDiego ML1, Chaves F1, Neumann G2, Kawaoka Y3, Sant AJ4.
Author information
1 Department of Microbiology and Immunology, D.H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642; and. 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, WI 53706. 3 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, WI 53706 yoshihiro.kawaoka@wisc.edu andrea_sant@urmc.rochester.edu. 4 Department of Microbiology and Immunology, D.H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642; and yoshihiro.kawaoka@wisc.edu andrea_sant@urmc.rochester.edu.
Abstract
Avian influenza vaccines exhibit poor immunogenicity in humans. We hypothesized that one factor underlying weak B cell responses was sequence divergence between avian and seasonal influenza hemagglutinin proteins, thus limiting the availability of adequate CD4 T cell help. To test this, a novel chimeric hemagglutinin protein (cH7/3) was derived, comprised of the stem domain from seasonal H3 hemagglutinin and the head domain from avian H7. Immunological memory to seasonal influenza was established in mice, through strategies that included seasonal inactivated vaccines, Flumist, and synthetic peptides derived from the H3 stalk domain. After establishment of memory, mice were vaccinated with H7 or cH7/3 protein. The cH7/3 Ag was able to recall H3-specific CD4 T cells, and this potentiated CD4 T cell response was associated with enhanced early germinal center response and rapid elicitation of Abs to H7, including Abs specific for the H7 head domain. These results suggest that in pandemic situations, inclusion of CD4 T cell epitopes from seasonal viruses have the potential to overcome the poor immunogenicity of avian vaccines by helping B cells and conferring greater subtype-specific Ab response to viral HA.
Copyright ? 2019 by The American Association of Immunologists, Inc.
PMID: 31399519 DOI: 10.4049/jimmunol.1900819
A Novel Vaccine Strategy to Overcome Poor Immunogenicity of Avian Influenza Vaccines through Mobilization of Memory CD4 T Cells Established by Seasonal Influenza.
DiPiazza AT1, Fan S2, Rattan A1, DeDiego ML1, Chaves F1, Neumann G2, Kawaoka Y3, Sant AJ4.
Author information
1 Department of Microbiology and Immunology, D.H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642; and. 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, WI 53706. 3 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, WI 53706 yoshihiro.kawaoka@wisc.edu andrea_sant@urmc.rochester.edu. 4 Department of Microbiology and Immunology, D.H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642; and yoshihiro.kawaoka@wisc.edu andrea_sant@urmc.rochester.edu.
Abstract
Avian influenza vaccines exhibit poor immunogenicity in humans. We hypothesized that one factor underlying weak B cell responses was sequence divergence between avian and seasonal influenza hemagglutinin proteins, thus limiting the availability of adequate CD4 T cell help. To test this, a novel chimeric hemagglutinin protein (cH7/3) was derived, comprised of the stem domain from seasonal H3 hemagglutinin and the head domain from avian H7. Immunological memory to seasonal influenza was established in mice, through strategies that included seasonal inactivated vaccines, Flumist, and synthetic peptides derived from the H3 stalk domain. After establishment of memory, mice were vaccinated with H7 or cH7/3 protein. The cH7/3 Ag was able to recall H3-specific CD4 T cells, and this potentiated CD4 T cell response was associated with enhanced early germinal center response and rapid elicitation of Abs to H7, including Abs specific for the H7 head domain. These results suggest that in pandemic situations, inclusion of CD4 T cell epitopes from seasonal viruses have the potential to overcome the poor immunogenicity of avian vaccines by helping B cells and conferring greater subtype-specific Ab response to viral HA.
Copyright ? 2019 by The American Association of Immunologists, Inc.
PMID: 31399519 DOI: 10.4049/jimmunol.1900819