Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India

Autor: Srikanth Tripathy, Shweta Chatrath, Sathyamurthy Pattabiram, Nikhil Singla, Jill Gilmour, Rajat Goyal, Philip Bergin, Soumya Swaminathan, Sivasankaran Munusamy Ponnan, Hanna Elizabeth Luke, Kannan Thiruvengadam, Joyeeta Mukherjee, Sriram Kumar, Sudha Subramaniam, Malathy Muthu, Jakub Kopycinski
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Physiology
T-Lymphocytes
HIV Infections
White Blood Cells
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Vaccines
DNA
Cytotoxic T cell
Public and Occupational Health
030212 general & internal medicine
Enzyme-Linked Immunoassays
Immune Response
AIDS Vaccines
Vaccines
Innate Immune System
Immunity
Cellular
Multidisciplinary
T Cells
ELISPOT
Viral Vaccine
Vaccination and Immunization
Healthy Volunteers
medicine.anatomical_structure
Infectious Diseases
Medicine
Cytokines
Female
Cellular Types
Research Article
Infectious Disease Control
Science
T cell
Immune Cells
Immunology
Immunization
Secondary
India
Cytotoxic T cells
Research and Analysis Methods
Peripheral blood mononuclear cell
Microbiology
03 medical and health sciences
Interferon-gamma
Immune system
Virology
medicine
Humans
Immunoassays
Blood Cells
business.industry
Viral vaccines
Tumor Necrosis Factor-alpha
Vaccine trial
HIV vaccines
Biology and Life Sciences
Cell Biology
Molecular Development
030104 developmental biology
Immune System
Immunologic Techniques
HIV-1
Interleukin-2
Preventive Medicine
business
CD8
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 3, p e0213911 (2019)
ISSN: 1932-6203
Popis: Effective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial infection of host cells or limit early events of viral dissemination. A Phase I HIV-1 prophylactic vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009.The trial tested a HIV-1 subtype C vaccine in a prime-boost regimen, comprising of a DNA prime (ADVAX) and Modified Vaccine Ankara (MVA) (TBC-M4) boost. The trial reported that the vaccine regimen was safe, well tolerated, and resulted in enhancement of HIV-specific immune responses. However, preliminary immunological studies were limited to vaccine-induced IFN-γ responses against the Env and Gag peptides. The present study is a retrospective study to characterize in detail the nature of the vaccine-induced cell mediated immune responses among volunteers, using Peripheral Blood Mononuclear Cells (PBMC) that were archived during the trial. ELISpot was used to measure IFN-γ responses and polyfunctional T cells were analyzed by intracellular multicolor flow cytometry. It was observed that DNA priming and MVA boosting induced Env and Gag specific bi-functional and multi-functional CD4+ and CD8+ T cells expressing IFN-γ, TNF-α and IL-2. The heterologous prime-boost regimen appeared to be slightly superior to the homologous prime-boost regimen in inducing favorable cell mediated immune responses. These results suggest that an in-depth analysis of vaccine-induced cellular immune response can aid in the identification of correlates of an effective immunogenic response, and inform future design of HIV vaccines.
Databáze: OpenAIRE
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