Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees

Gamal A. Elmowalid, Ming Qiao, Sook Hyang Jeong, Brian B. Borg, Thomas F. Baumert, Ronda K. Sapp, Zongyi Hu, Krishna Murthy, T. Jake Liang

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Recombinant hepatitis C virus (HCV)-like particles (HCV-LPs) containing HCV structural proteins (core, E1, and E2) produced in insect cells resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice and baboons. Here, we present evidence on the immunogenicity and induction of protective immunity by HCV-LPs in chimpanzees. Chimpanzees (two in each group), were immunized with HCV-LPs or HCV-LPs plus AS01B adjuvant. After immunizations, all animals developed an HCV-specific immune response including IFN-γ+, IL-2+, CD4 +, and CD8+ T cell and proliferative lymphocyte responses against core, E1, and E2. Upon challenge with an infectious HCV inoculum, one chimpanzee developed transient viremia with low HCV RNA titers (103 to 104 copies per ml) in the third and fourth weeks after the challenge. The three other chimpanzees became infected with higher levels of viremia (104 to 105 copies per ml), but their viral levels became unquantifiable (<103 copies per ml) 10 weeks after the challenge. After the HCV challenge, all four chimpanzees demonstrated a significant increase in peripheral and intrahepatic T cell and proliferative responses against the HCV structural proteins. These T cell responses coincided with the fall in HCV RNA levels. Four naïve chimpanzees were infected with the same HCV inoculum, and three developed persistent infection with higher viremia in the range of 105 to 106 copies per ml. Our study suggests that HCV-LP immunization induces HCV-specific cellular immune responses that can control HCV challenge in the chimpanzee model.

Original languageEnglish
Pages (from-to)8427-8432
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number20
DOIs
StatePublished - 15 May 2007

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Pan troglodytes
Virus Diseases
Hepacivirus
Virion
Immunization
Viremia
Viral Structural Proteins
T-Lymphocytes
Cellular Immunity
Animal Hepatitis
Hepatovirus
RNA
Papio
Humoral Immunity
Viral Load

Keywords

  • Envelope proteins
  • Prevention
  • Protective immunity
  • Vaccine
  • Viral clearance

Cite this

Elmowalid, Gamal A. ; Qiao, Ming ; Jeong, Sook Hyang ; Borg, Brian B. ; Baumert, Thomas F. ; Sapp, Ronda K. ; Hu, Zongyi ; Murthy, Krishna ; Liang, T. Jake. / Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 20. pp. 8427-8432.
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abstract = "Recombinant hepatitis C virus (HCV)-like particles (HCV-LPs) containing HCV structural proteins (core, E1, and E2) produced in insect cells resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice and baboons. Here, we present evidence on the immunogenicity and induction of protective immunity by HCV-LPs in chimpanzees. Chimpanzees (two in each group), were immunized with HCV-LPs or HCV-LPs plus AS01B adjuvant. After immunizations, all animals developed an HCV-specific immune response including IFN-γ+, IL-2+, CD4 +, and CD8+ T cell and proliferative lymphocyte responses against core, E1, and E2. Upon challenge with an infectious HCV inoculum, one chimpanzee developed transient viremia with low HCV RNA titers (103 to 104 copies per ml) in the third and fourth weeks after the challenge. The three other chimpanzees became infected with higher levels of viremia (104 to 105 copies per ml), but their viral levels became unquantifiable (<103 copies per ml) 10 weeks after the challenge. After the HCV challenge, all four chimpanzees demonstrated a significant increase in peripheral and intrahepatic T cell and proliferative responses against the HCV structural proteins. These T cell responses coincided with the fall in HCV RNA levels. Four na{\"i}ve chimpanzees were infected with the same HCV inoculum, and three developed persistent infection with higher viremia in the range of 105 to 106 copies per ml. Our study suggests that HCV-LP immunization induces HCV-specific cellular immune responses that can control HCV challenge in the chimpanzee model.",
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Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. / Elmowalid, Gamal A.; Qiao, Ming; Jeong, Sook Hyang; Borg, Brian B.; Baumert, Thomas F.; Sapp, Ronda K.; Hu, Zongyi; Murthy, Krishna; Liang, T. Jake.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 20, 15.05.2007, p. 8427-8432.

Research output: Contribution to journalArticle

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AU - Elmowalid, Gamal A.

AU - Qiao, Ming

AU - Jeong, Sook Hyang

AU - Borg, Brian B.

AU - Baumert, Thomas F.

AU - Sapp, Ronda K.

AU - Hu, Zongyi

AU - Murthy, Krishna

AU - Liang, T. Jake

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AB - Recombinant hepatitis C virus (HCV)-like particles (HCV-LPs) containing HCV structural proteins (core, E1, and E2) produced in insect cells resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice and baboons. Here, we present evidence on the immunogenicity and induction of protective immunity by HCV-LPs in chimpanzees. Chimpanzees (two in each group), were immunized with HCV-LPs or HCV-LPs plus AS01B adjuvant. After immunizations, all animals developed an HCV-specific immune response including IFN-γ+, IL-2+, CD4 +, and CD8+ T cell and proliferative lymphocyte responses against core, E1, and E2. Upon challenge with an infectious HCV inoculum, one chimpanzee developed transient viremia with low HCV RNA titers (103 to 104 copies per ml) in the third and fourth weeks after the challenge. The three other chimpanzees became infected with higher levels of viremia (104 to 105 copies per ml), but their viral levels became unquantifiable (<103 copies per ml) 10 weeks after the challenge. After the HCV challenge, all four chimpanzees demonstrated a significant increase in peripheral and intrahepatic T cell and proliferative responses against the HCV structural proteins. These T cell responses coincided with the fall in HCV RNA levels. Four naïve chimpanzees were infected with the same HCV inoculum, and three developed persistent infection with higher viremia in the range of 105 to 106 copies per ml. Our study suggests that HCV-LP immunization induces HCV-specific cellular immune responses that can control HCV challenge in the chimpanzee model.

KW - Envelope proteins

KW - Prevention

KW - Protective immunity

KW - Vaccine

KW - Viral clearance

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