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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 [PLoS One] 2017 Oct 24; Vol. 12 (10), pp. e0186602. Date of Electronic Publication: 2017 Oct 24 (Print Publication: 2017). - Publication Year :
- 2017
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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.<br />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.<br />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.<br />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.<br />Trial Registration: ClinicalTrials.gov NCT01923610.
- Subjects :
- AIDS Vaccines adverse effects
Antibodies, Neutralizing immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
HIV Antibodies blood
Healthy Volunteers
Humans
Placebos
AIDS Vaccines immunology
HIV-1 immunology
Immunization, Secondary
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 29065142
- Full Text :
- https://doi.org/10.1371/journal.pone.0186602