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 - 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
SN - 0022-1899
VL - 216
SP - 153
EP - 161
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -