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Immune Restoration by TIGIT Blockade is Insufficient to Control Chronic SIV Infection

Webb et al., Journal of Virology. 2024.

https://pubmed.ncbi.nlm.nih.gov/38775481/

T-cell exhaustion from prolonged upregulation of immune checkpoint receptors (ICR) contributes to immune dysfunction and viral persistence of both human and simian immunodeficiency virus (HIV/SIV) infection. Previous in vitro research has demonstrated the potential use of ICR blockade as a therapeutic. Researchers used a monoclonal antibody targeting humanized T cell immunoreceptor with Ig and ITIM domain (TIGIT) in male and female cynomolgus macaque and female rhesus macaque SIV models, 4–14 years of age. TIGIT blockade was well tolerated, with moderately increased proliferation of T cells and natural killer cells, but a reduction in plasma viral load was not observed. Future research to eliminate SIV should combine ICR blockades with other immunotherapies. Supported by ORIP (P51OD011092), NIAID, and NIMH.

SIV-Specific Antibodies Protect Against Inflammasome-Driven Encephalitis in Untreated Macaques

Castell et al., Cell Reports. 2024.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11552693

Viral infections are the most common infectious cause of encephalitis, and simian immunodeficiency virus (SIV)–infected macaques are a well-established model for HIV. Researchers investigated the protective effects of SIV-specific antibodies against inflammation-driven encephalitis in using untreated, SIV-infected, male and female pigtail and rhesus macaques. Findings indicate that these antibodies reduce neuroinflammation and encephalitis, highlighting the importance of antibodies in controlling neuroimmune responses, especially in the absence of antiretroviral therapy. This study provides insight into immune-modulatory approaches to combating inflammation-driven encephalopathies. Supported by ORIP (U42OD013117, T32OD011089), NIDA, NHLBI, NIAID, NINDS, and NIMH.

RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology

Huang et al., The Journal of Infectious Diseases. 2024.

https://pubmed.ncbi.nlm.nih.gov/38079216/

Brain tissue–derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in HIV CNS pathology. Using brain homogenate (BH) and bdEVs from male pigtailed macaques, researchers identified dysregulated RNAs in acute and chronic infection. Most dysregulated messenger RNAs (mRNAs) in bdEVs reflected dysregulation in source BH, and these mRNAs are disproportionately involved in inflammation and immune responses. Additionally, several circular RNAs were differentially abundant in source tissue and might be responsible for specific differences in small RNA levels in bdEVs during simian immunodeficiency virus (SIV) infection. This RNA profiling shows potential regulatory networks in SIV infection and SIV-related CNS pathology. Supported by ORIP (U42OD013117), NCI, NIAID, NIDA, NIMH, and NINDS.

Neutralizing Antibody Response to SARS‐CoV‐2 Bivalent mRNA Vaccine in SIV‐Infected Rhesus Macaques: Enhanced Immunity to XBB Subvariants by Two‐Dose Vaccination

Faraone, Journal of Medical Virology. 2024.

https://pubmed.ncbi.nlm.nih.gov/38528837/

Researchers have shown that mRNA vaccination is less effective for people with advanced or untreated HIV infection, but data on the efficacy of mRNA vaccination against SARS-CoV-2 in this population are limited. Using rhesus macaques (sex not specified) with simian immunodeficiency virus (SIV), investigators examined the neutralizing antibody (nAb) response to SARS-CoV-2 vaccination. They found that administration of the bivalent vaccine alone can generate robust nAb titers against Omicron subvariants. Additionally, dams that received antiretroviral therapy had lower nAb titers than untreated dams. Overall, these findings highlight the need for further investigations into the nAb response in people with HIV. Supported by ORIP (P51OD011104), NCI, NIAID, NICHD, and NIMH.