Rhesus Macaques Studies Reveal Promising Vaccine Approach for HIV
2011-05-11
The vaccine showed promise in protecting the rhesus macaque against SIV
Credit: Oregon Health & Science University
As reported in the online edition of Nature on May 11, 2011, research conducted at Oregon Health & Science University's Vaccine and Gene Therapy Institute (VGTI) has developed a new vaccine that can protect rhesus macaques against simian immunodeficiency virus (SIV), the monkey equivalent of HIV, and could contribute to the development of an effective HIV/AIDS vaccine.
For details, refer to the publication:
Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature (2011) doi: 10.1038/nature10003.Scott G. Hansen, Julia C. Ford, Matthew S. Lewis, Abigail B. Ventura, Colette M. Hughes, Lia Coyne-Johnson,Nathan Whizin, Kelli Oswald, Rebecca Shoemaker,Tonya Swanson, Alfred W. Legasse, Maria J. Chiuchiolo, Christopher L. Parks, Michael K. Axthelm, Jay A. Nelson, Michael A. Jarvis, Michael Piatak, Jeffrey D. Lifson & Louis J. Picker
Abstract:
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 mechanisms1, 2, 3. 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 control4. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors5 establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (TEM) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIVMAC239 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 TEM responses might significantly contribute to an efficacious HIV/AIDS vaccine.
