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Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization
- Source :
- PLoS ONE, Repisalud, Instituto de Salud Carlos III (ISCIII), PLoS ONE, Vol 12, Iss 10, p e0186602 (2017), Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Dipòsit Digital de la UB, Universidad de Barcelona
- Publication Year :
- 2016
-
Abstract
- BACKGROUND: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. RESULTS: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. CONCLUSIONS: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923610. This study was partially supported by grants: FIS PI12/00969, PI15/00480, SAF2015-66193-R., EC10-153, TRA-094, RIS, HIVACAT, SAF2013-45232-R. RIS: Red Temática Cooperativa de Grupos de Investigación en Sida del Fondo de Investigación Sanitaria (FIS). HIVACAT: HIV development program in Catalonia. IDIBAPS: Institut d’Investigacions Biomèdiques August Pi I Sunyer. Sí
- Subjects :
- 0301 basic medicine
RNA viruses
CD4-Positive T-Lymphocytes
Physiology
viruses
Human immunodeficiency virus (HIV)
lcsh:Medicine
Antibody Response
CD8-Positive T-Lymphocytes
HIV Antibodies
medicine.disease_cause
Pathology and Laboratory Medicine
Biochemistry
Placebos
White Blood Cells
Immunodeficiency Viruses
Animal Cells
Immune Physiology
Healthy volunteers
Medicine and Health Sciences
Medicine
Public and Occupational Health
Enzyme-Linked Immunoassays
Sida
lcsh:Science
Immune Response
AIDS Vaccines
Multidisciplinary
Immune System Proteins
biology
T Cells
MVA-B
Flow Cytometry
Vaccination and Immunization
Healthy Volunteers
Cèl·lules T
Medical Microbiology
Viral Pathogens
Viruses
Cellular Types
Pathogens
Research Article
Immune Cells
Immunology
T cells
Immunization, Secondary
Cytotoxic T cells
Enzyme-Linked Immunosorbent Assay
Research and Analysis Methods
complex mixtures
Microbiology
Antibodies
03 medical and health sciences
Immune system
Vacunes antivíriques
Retroviruses
VIH (Virus)
Humans
Immunoassays
Microbial Pathogens
Blood Cells
business.industry
HIV (Viruses)
Viral vaccines
lcsh:R
Lentivirus
Organisms
Biology and Life Sciences
Proteins
HIV
Correction
Cell Biology
biology.organism_classification
Virology
Antibodies, Neutralizing
030104 developmental biology
Immunization
Immunologic Techniques
HIV-1
lcsh:Q
Preventive Medicine
business
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....1fb23d66b20703b751c30c71715e3440