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Assessment Of Human Cd4+ And Cd8+ T Lymphocyte Responses In Experimental Viral Vaccine Studies, Alan Rothman, Y. Yamada, Julie Jameson, John Cruz, Kim West, Sharone Green, Francis Ennis
Assessment Of Human Cd4+ And Cd8+ T Lymphocyte Responses In Experimental Viral Vaccine Studies, Alan Rothman, Y. Yamada, Julie Jameson, John Cruz, Kim West, Sharone Green, Francis Ennis
Alan Rothman
The traditional in vitro correlate of immunological protection is the induction by a vaccine of neutralizing antibodies against the virus. It was formerly assumed that protection induced by a vaccine was solely due to neutralizing antibodies. Neutralizing antibodies are potent in the prevention of certain diseases, but virus-specific CD4+ T helper cells aid in the proliferation of specific antigen-triggered B cells to make antibodies. CD8+ T cells are responsible for eliminating virus-infected cells during viral illness, and may act as a second line of defence by becoming activated and eliminating any cells that become infected despite the presence of neutralizing …
Altered Cytokine Responses Of Dengue-Specific Cd4+ T Cells To Heterologous Serotypes, Maloy Mangada, Alan Rothman
Altered Cytokine Responses Of Dengue-Specific Cd4+ T Cells To Heterologous Serotypes, Maloy Mangada, Alan Rothman
Alan Rothman
The interplay of different inflammatory cytokines induced during a dengue (DEN) virus infection plays a role in either protection or increased disease severity. We measured the frequencies and characterized the cytokine responses of DEN virus-specific memory CD4+ T cells in PBMC of six volunteers who received experimental live attenuated monovalent DEN vaccines. IFN-gamma and TNF-alpha responses to inactivated DEN Ags were detected in up to 0.54 and 1.17% of total circulating CD4+ T cells, respectively. Ags from the homologous serotype elicited the highest IFN-gamma response. The ratio of TNF-alpha- to IFN-gamma-producing CD4+ T cells was higher after stimulation with Ags …
Dominant Recognition By Human Cd8+ Cytotoxic T Lymphocytes Of Dengue Virus Nonstructural Proteins Ns3 And Ns1.2a, Anuja Mathew, Ichiro Kurane, Alan Rothman, Lingling Zeng, Margo Brinton, Francis Ennis
Dominant Recognition By Human Cd8+ Cytotoxic T Lymphocytes Of Dengue Virus Nonstructural Proteins Ns3 And Ns1.2a, Anuja Mathew, Ichiro Kurane, Alan Rothman, Lingling Zeng, Margo Brinton, Francis Ennis
Alan Rothman
A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the …
Robust Intrapulmonary Cd8 T Cell Responses And Protection With An Attenuated N1l Deleted Vaccinia Virus, Anuja Mathew, Joel O'Bryan, William L. Marshall, Girish J. Kotwal, Masanori Terajima, Sharone Green, Alan L. Rothman, Francis A. Ennis
Robust Intrapulmonary Cd8 T Cell Responses And Protection With An Attenuated N1l Deleted Vaccinia Virus, Anuja Mathew, Joel O'Bryan, William L. Marshall, Girish J. Kotwal, Masanori Terajima, Sharone Green, Alan L. Rothman, Francis A. Ennis
Alan Rothman
BACKGROUND: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated …
Identification Of Murine Poxvirus-Specific Cd8+ Ctl Epitopes With Distinct Functional Profiles, Anuja Mathew, Masanori Terajima, Kim West, Sharone Green, Alan Rothman, Francis Ennis, Jeffrey Kennedy
Identification Of Murine Poxvirus-Specific Cd8+ Ctl Epitopes With Distinct Functional Profiles, Anuja Mathew, Masanori Terajima, Kim West, Sharone Green, Alan Rothman, Francis Ennis, Jeffrey Kennedy
Alan Rothman
Murine T cell epitopes against vaccinia virus (VV) have not been characterized to date in part due to the large and complex genome of VV. We have identified and characterized two CD8+ T cell epitopes on the A47L (modified VV Ankara strain (MVA)-029) and J6R (MVA-043) proteins of VV that are Db and Kb restricted, respectively. Following i.p. immunization with VV New York City Board of Health (NYCBH) strain, MVA-029 peptide-stimulated splenocytes secreted IFN-gamma from 7 days to 7 mo postimmunization, and virus-stimulated effectors were also able to lyse MVA-029-pulsed target cells at the same time points. In contrast, MVA-043 …