Linked Life Data

21562493

Source:http://linkedlifedata.com/resource/pubmed/id/21562493

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7348
pubmed:dateCreated
2011-5-26
pubmed:abstractText
The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (?1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
473
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
523-7
pubmed:dateRevised
2011-9-14
pubmed:meshHeading
pubmed-meshheading:21562493-AIDS Vaccines, pubmed-meshheading:21562493-Animals, pubmed-meshheading:21562493-CD4-Positive T-Lymphocytes, pubmed-meshheading:21562493-CD8-Positive T-Lymphocytes, pubmed-meshheading:21562493-Cytomegalovirus, pubmed-meshheading:21562493-DNA, Viral, pubmed-meshheading:21562493-Genetic Vectors, pubmed-meshheading:21562493-Immunity, Mucosal, pubmed-meshheading:21562493-Immunologic Memory, pubmed-meshheading:21562493-Macaca mulatta, pubmed-meshheading:21562493-Male, pubmed-meshheading:21562493-RNA, Viral, pubmed-meshheading:21562493-SAIDS Vaccines, pubmed-meshheading:21562493-Simian Acquired Immunodeficiency Syndrome, pubmed-meshheading:21562493-Simian immunodeficiency virus, pubmed-meshheading:21562493-T-Lymphocytes, pubmed-meshheading:21562493-Time Factors, pubmed-meshheading:21562493-Vaccines, DNA, pubmed-meshheading:21562493-Viral Load, pubmed-meshheading:21562493-Virus Replication
pubmed:year
2011
pubmed:articleTitle
Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine.
pubmed:affiliation
Vaccine and Gene Therapy Institute, Department of Molecular Microbiology, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural