التفاصيل البيبلوغرافية
| العنوان: |
First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens. |
| المؤلفون: |
Nyombayire, Julien, Anzala, Omu, Gazzard, Brian, Karita, Etienne, Bergin, Philip, Hayes, Peter, Kopycinski, Jakub, Omosa-Manyonyi, Gloria, Jackson, Akil, Bizimana, Jean, Farah, Bashir, Sayeed, Eddy, Parks, Christopher L., Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Dally, Len, Barin, Burc |
| المصدر: |
Journal of Infectious Diseases; Jan2017, Vol. 215 Issue 1, p95-104, 10p |
| مصطلحات موضوعية: |
SENDAI virus diseases, RNA virus infections, T-cell lymphoma, ANTIBODY formation, REVERSE transcriptase, HIV prevention, INTRANASAL medication, AIDS vaccines, CELLULAR immunity, CLINICAL trials, COMPARATIVE studies, GENES, HIV, HIV infections, IMMUNIZATION, RESEARCH methodology, MEDICAL cooperation, PARAMYXOVIRUSES, RESEARCH, T cells, VACCINES, VIRAL antibodies, EVALUATION research, RANDOMIZED controlled trials, PHYSIOLOGY |
| مصطلحات جغرافية: |
KENYA, RWANDA |
| مستخلص: |
Background: We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.Methods: Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH).Results: All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic.Conclusions: SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody responses. The prime-boost sequence appears to determine which arm of the immune response is stimulated.Clinical Trials Registration: NCT01705990. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Infectious Diseases is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
