PMID- 19918060
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20211028
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 47
DP  - 2009 Nov 24
TI  - Adenovirus vector vaccination induces expansion of memory CD4 T cells with a 
      mucosal homing phenotype that are readily susceptible to HIV-1.
PG  - 19940-5
LID - 10.1073/pnas.0907898106 [doi]
AB  - In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that 
      were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 
      infection on vaccination with an Ad5 vaccine. We propose that this was due to 
      activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To 
      test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy 
      volunteers. Dendritic cells (DCs) from these individuals were pulsed with 
      replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. 
      Cytokine profiles, proliferative capacity, mucosal migration potential, and 
      susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells 
      were measured. Stimulation of T cells from healthy Ad5-seropositive but 
      Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors 
      induced preferential expansion of adenovirus memory CD4 T cells expressing 
      alpha(4)beta(7) integrins and CCR9, indicating a mucosal-homing phenotype. CD4 
      T-cell proliferation and IFN-gamma production in response to Ad stimulation 
      correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate 
      with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and 
      Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher 
      susceptibility to infection by R5 tropic HIV-1. This suggests that 
      adenoviral-based vaccination against HIV-1 in individuals with preexisting 
      immunity against Ad5 results in preferential expansion of HIV-susceptible 
      activated CD4 T cells that home to mucosal tissues, increases the number of virus 
      targets, and leads to a higher susceptibility to HIV acquisition.
FAU - Benlahrech, Adel
AU  - Benlahrech A
AD  - Department of Immunology, Imperial College London, Chelsea and Westminster 
      Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom.
FAU - Harris, Julian
AU  - Harris J
FAU - Meiser, Andrea
AU  - Meiser A
FAU - Papagatsias, Timos
AU  - Papagatsias T
FAU - Hornig, Julia
AU  - Hornig J
FAU - Hayes, Peter
AU  - Hayes P
FAU - Lieber, Andre
AU  - Lieber A
FAU - Athanasopoulos, Takis
AU  - Athanasopoulos T
FAU - Bachy, Veronique
AU  - Bachy V
FAU - Csomor, Eszter
AU  - Csomor E
FAU - Daniels, Rod
AU  - Daniels R
FAU - Fisher, Kerry
AU  - Fisher K
FAU - Gotch, Frances
AU  - Gotch F
FAU - Seymour, Len
AU  - Seymour L
FAU - Logan, Karen
AU  - Logan K
FAU - Barbagallo, Romina
AU  - Barbagallo R
FAU - Klavinskis, Linda
AU  - Klavinskis L
FAU - Dickson, George
AU  - Dickson G
FAU - Patterson, Steven
AU  - Patterson S
LA  - eng
GR  - 11339/CRUK_/Cancer Research UK/United Kingdom
GR  - G0200284/MRC_/Medical Research Council/United Kingdom
GR  - G0501957/MRC_/Medical Research Council/United Kingdom
GR  - G0100482/MRC_/Medical Research Council/United Kingdom
GR  - MC_U117531986/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091116
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (AIDS Vaccines)
RN  - 0 (Antibodies, Viral)
RN  - 0 (CC chemokine receptor 9)
RN  - 0 (CCR4 protein, human)
RN  - 0 (Integrin beta Chains)
RN  - 0 (Receptors, CCR)
RN  - 0 (Receptors, CCR4)
RN  - 0 (integrin beta7)
RN  - 143198-26-9 (Integrin alpha4)
SB  - IM
MH  - AIDS Vaccines/immunology
MH  - Adenoviridae/genetics/*immunology
MH  - Antibodies, Viral/immunology
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - Dendritic Cells/cytology/immunology
MH  - Genetic Vectors/genetics/immunology
MH  - HIV Infections/immunology
MH  - HIV-1/*immunology/pathogenicity
MH  - Humans
MH  - Immunity, Mucosal/*immunology
MH  - Immunologic Memory/*immunology
MH  - Integrin alpha4/immunology
MH  - Integrin beta Chains/immunology
MH  - Lymphocyte Activation/immunology
MH  - Mucous Membrane/immunology
MH  - Phenotype
MH  - Receptors, CCR/immunology
MH  - Receptors, CCR4/immunology
MH  - *Vaccination
PMC - PMC2785271
COIS- The authors declare no conflict of interest.
EDAT- 2009/11/18 06:00
MHDA- 2010/01/15 06:00
PMCR- 2010/05/24
CRDT- 2009/11/18 06:00
PHST- 2009/11/18 06:00 [entrez]
PHST- 2009/11/18 06:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
PHST- 2010/05/24 00:00 [pmc-release]
AID - 0907898106 [pii]
AID - 0317 [pii]
AID - 10.1073/pnas.0907898106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19940-5. doi: 
      10.1073/pnas.0907898106. Epub 2009 Nov 16.