TY - JOUR
T1 - Characterizing the cellular immune response to parainfluenza virus 3
AU - Aguayo-Hiraldo, Paibel I.
AU - Arasaratnam, Reuben J.
AU - Tzannou, Ifigeneia
AU - Kuvalekar, Manik
AU - Lulla, Premal
AU - Naik, Swati
AU - Martinez, Caridad A.
AU - Piedra, Pedro A.
AU - Vera, Juan F.
AU - Leen, Ann M.
N1 - Funding Information:
Financial support. This work was supported by the Flow Cytometry and Cell and Vector Production shared resources in the Dan L. Duncan Comprehensive Cancer Center (support grant P30 CA125123). R. J. A. and P. I. A.-H. are supported by the National Institutes of Health (grant numbers T32 DK060445-11 and T32 HL92332-12, respectively). J. F. V. is supported by a Mentored Research Scholars Grant in Applied and Clinical Research (grant number MRSG-14-197-01-LIB) from the American Cancer Society.
Publisher Copyright:
© The Author 2017.
PY - 2017/7/15
Y1 - 2017/7/15
N2 - Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4+ and CD8+ T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.
AB - Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4+ and CD8+ T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.
KW - Immunotherapy
KW - Parainfluenza virus 3
KW - Virus-specific T cells
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U2 - 10.1093/infdis/jix203
DO - 10.1093/infdis/jix203
M3 - Article
C2 - 28472480
AN - SCOPUS:85028438315
VL - 216
SP - 153
EP - 161
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
SN - 0022-1899
IS - 2
ER -