PMID- 29065142
OWN - NLM
STAT- MEDLINE
DCOM- 20171113
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 10
DP  - 2017
TI  - Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following 
      a late MVA-B boost 4 years after the last immunization.
PG  - e0186602
LID - 10.1371/journal.pone.0186602 [doi]
LID - e0186602
AB  - 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-gamma 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.
FAU - Guardo, Alberto C
AU  - Guardo AC
AD  - Immunopathology and Cellular Immunology, AIDS Research Group, IDIBAPS, Hospital 
      Clinic, University of Barcelona, Barcelona, Spain.
FAU - Gomez, Carmen Elena
AU  - Gomez CE
AD  - Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.
FAU - Diaz-Brito, Vicens
AU  - Diaz-Brito V
AD  - Infectious Diseases Unit, Hospital Clinic, IDIBAPS, University of Barcelona, 
      Spain.
FAU - Pich, Judit
AU  - Pich J
AD  - Infectious Diseases Unit, Hospital Clinic, IDIBAPS, University of Barcelona, 
      Spain.
FAU - Arnaiz, Joan Albert
AU  - Arnaiz JA
AD  - Infectious Diseases Unit, Hospital Clinic, IDIBAPS, University of Barcelona, 
      Spain.
FAU - Perdiguero, Beatriz
AU  - Perdiguero B
AD  - Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.
FAU - Garcia-Arriaza, Juan
AU  - Garcia-Arriaza J
AD  - Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.
FAU - Gonzalez, Nuria
AU  - Gonzalez N
AD  - AIDS Immunopathogenesis Unit, Centro Nacional de Microbiologia, Instituto de 
      Salud Carlos III, Madrid, Spain.
FAU - Sorzano, Carlos O S
AU  - Sorzano COS
AD  - Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.
FAU - Jimenez, Laura
AU  - Jimenez L
AD  - AIDS Immunopathogenesis Unit, Centro Nacional de Microbiologia, Instituto de 
      Salud Carlos III, Madrid, Spain.
FAU - Jimenez, Jose Luis
AU  - Jimenez JL
AD  - Seccion Inmunologia, Laboratorio InmunoBiologia Molecular, Hospital General 
      Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio 
      Maranon (IISGM), Spanish HIV HGM Biobank, Networking Research Center on 
      Bioengineering, Biomaterials & Nanomedicine (CIBERBBN), Madrid, Spain.
FAU - Munoz-Fernandez, Maria Angeles
AU  - Munoz-Fernandez MA
AD  - Seccion Inmunologia, Laboratorio InmunoBiologia Molecular, Hospital General 
      Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio 
      Maranon (IISGM), Spanish HIV HGM Biobank, Networking Research Center on 
      Bioengineering, Biomaterials & Nanomedicine (CIBERBBN), Madrid, Spain.
FAU - Gatell, Jose M
AU  - Gatell JM
AD  - Infectious Diseases Unit, Hospital Clinic, IDIBAPS, University of Barcelona, 
      Spain.
FAU - Alcami, Jose
AU  - Alcami J
AD  - AIDS Immunopathogenesis Unit, Centro Nacional de Microbiologia, Instituto de 
      Salud Carlos III, Madrid, Spain.
FAU - Esteban, Mariano
AU  - Esteban M
AD  - Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.
FAU - Lopez Bernaldo de Quiros, Juan Carlos
AU  - Lopez Bernaldo de Quiros JC
AD  - Seccion Inmunologia, Laboratorio InmunoBiologia Molecular, Hospital General 
      Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio 
      Maranon (IISGM), Spanish HIV HGM Biobank, Networking Research Center on 
      Bioengineering, Biomaterials & Nanomedicine (CIBERBBN), Madrid, Spain.
FAU - Garcia, Felipe
AU  - Garcia F
AD  - Infectious Diseases Unit, Hospital Clinic, IDIBAPS, University of Barcelona, 
      Spain.
FAU - Plana, Montserrat
AU  - Plana M
AUID- ORCID: 0000-0002-0767-4329
AD  - Immunopathology and Cellular Immunology, AIDS Research Group, IDIBAPS, Hospital 
      Clinic, University of Barcelona, Barcelona, Spain.
CN  - RISVAC02boost study
LA  - eng
SI  - ClinicalTrials.gov/NCT01923610
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20171024
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (AIDS Vaccines)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (HIV Antibodies)
RN  - 0 (Placebos)
SB  - IM
EIN - PLoS One. 2018 Apr 10;13(4):e0195915. PMID: 29634751
MH  - AIDS Vaccines/adverse effects/*immunology
MH  - Antibodies, Neutralizing/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - HIV Antibodies/blood
MH  - HIV-1/*immunology
MH  - Healthy Volunteers
MH  - Humans
MH  - *Immunization, Secondary
MH  - Placebos
PMC - PMC5655491
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/10/25 06:00
MHDA- 2017/11/14 06:00
PMCR- 2017/10/24
CRDT- 2017/10/25 06:00
PHST- 2016/12/15 00:00 [received]
PHST- 2017/09/10 00:00 [accepted]
PHST- 2017/10/25 06:00 [entrez]
PHST- 2017/10/25 06:00 [pubmed]
PHST- 2017/11/14 06:00 [medline]
PHST- 2017/10/24 00:00 [pmc-release]
AID - PONE-D-16-47067 [pii]
AID - 10.1371/journal.pone.0186602 [doi]
PST - epublish
SO  - PLoS One. 2017 Oct 24;12(10):e0186602. doi: 10.1371/journal.pone.0186602. 
      eCollection 2017.